Asia Pacific and Russia diagnostic study for EGFR testing - IGNITE

Study identifier:D7913C00074

ClinicalTrials.gov identifier:NCT01788163

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A diagnostic study to determine the prevalence of EGFR mutations in Asian and Russian patients with advanced NSCLC of Adenocarcinoma and Non-adenocarcinoma histologies

Medical condition

EGFR mutation status in aNSCLC patients (locally advanced and/or metastatic disease) with adenocarcinoma and non-adenocarcinoma histologies.

Phase

N/A

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

3500

Study type

Interventional

Age

18 Years +

Date

Study Start Date: 27 Feb 2013

Primary Completion Date: 25 Aug 2014

Study Completion Date: 20 Jun 2016

Study design

Allocation: N/A
Endpoint Classification: N/A
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic

Verification:

Verified 01 Oct 2017 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Tamworth, NSW, Australia

Location

Research Site

Tweed Heads, NSW, Australia

Location

Research Site

Wahroonga, NSW, Australia

Location

Research Site

Concord, NSW, Australia

Location

Research Site

Murdoch, WA, Australia

Location

Research Site

Woolloongabba, QLD, Australia

Location

Research Site

Campbelltown, NSW, Australia

Location

Research Site

Coffs Harbour, NSW, Australia

Arms	Assigned Interventions
Other: Locally advanced/metastatic NSCLC pats. Patients with locally advanced (stage IIIA/B) or metastatic NSCLC who have not received any local or systemic chemotherapy, and are not eligible for curative treatment (including surgery and chemoradiotherapy)	Genetic: EGFR mutation test EGFR mutation being tested in tissue and blood Other Name: Determination of EGFR mutation done at the Pathology lab

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Males or females that had Stage IIIB or Stage IV adenocarcinoma of the lung and who were systemic treatment naive or patients with recurrent disease who have previously received adjuvant chemotherapy were enrolled 27 February 2013 and 25 July 2014. The study was carried out in Asiapac countries and Russia.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 3500 patients were initially enrolled, of which 118 patients were enrolled but were excluded from the study upon failure to satisfy all eligibility criteria. These patients were not included in any analysis data sets.

Reporting Groups

	Description
China	Subjects in China that meet Inclusion/Exclusion (I/E) and population criteria.
Taiwan	Subjects in Taiwan that meet I/E and population criteria
South Korea	Subjects in South Korea that meet I/E and population criteria
Australia	Subjects in Australia that meet I/E and population criteria
Thailand	Subjects in Thailand that meet I/E and population criteria
Singapore	Subjects in Singapore that meet I/E and population criteria
Malaysia	Subjects in Malaysia that meet I/E and population criteria
Indonesia	Subjects in Indonesia that meet I/E and population criteria
Russia	Subjects in Russia that meet I/E and population criteria

Participant Flow: Overall Study

	China	Taiwan	South Korea	Australia	Thailand	Singapore	Malaysia	Indonesia	Russia
STARTED	1458	271	62	71	94	102	50	302	972
COMPLETED	1403	271	62	71	94	95	49	254	956
NOT COMPLETED	55	0	0	0	0	7	1	48	16
Unknown	53	0	0	0	0	7	1	48	15
Withdrawal by Subject	2	0	0	0	0	0	0	0	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
China	Subjects in China that meet I/E and population criteria.
Taiwan	Subjects in Taiwan that meet I/E and population criteria
South Korea	Subjects in South Korea that meet I/E and population criteria
Australia	Subjects in Australia that meet I/E and population criteria
Thailand	Subjects in Thailand that meet I/E and population criteria
Singapore	Subjects in Singapore that meet I/E and population criteria
Malaysia	Subjects in Malaysia that meet I/E and population criteria
Indonesia	Subjects in Indonesia that meet I/E and population criteria
Russia	Subjects in Russia that meet I/E and population criteria

Baseline Measures

	China	Taiwan	South Korea	Australia	Thailand	Singapore	Malaysia	Indonesia	Russia	Total
Number of Participants [units: Participants]	1458	271	62	71	94	102	50	302	972	3382
Age Continuous ^[1] [units: Years] Mean ± Standard Deviation Age (years)	59.8 ± 10.57	66.4 ± 12.66	65.9 ± 11.91	67.1 ± 10.02	61.2 ± 12.3	63.3 ± 10.79	58.7 ± 10.5	57.1 ± 11.46	59.8 ± 8.9	60.4 ± 10.73
Gender, Male/Female ^[2] [units: Participants]
Female	535	111	22	36	40	42	14	97	245	1142
Male	923	160	40	35	54	60	36	205	727	2240

Outcome Measures

1. Primary Outcome Measure: Overall Tumour Epidermal Growth Factor Receptor (EGFR) Mutation Status [ Time Frame: At Screening ]

Measure Type	Primary
Measure Name	Overall Tumour Epidermal Growth Factor Receptor (EGFR) Mutation Status
Measure Description	The 95% Confidence intervals were calculated using Clopper Pearson method for each country.
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Tumour Evaluable Population

Reporting Groups

	Description
China	Subjects in China that meet I/E and population criteria.
Taiwan	Subjects in Taiwan that meet I/E and population criteria
South Korea	Subjects in South Korea that meet I/E and population criteria
Australia	Subjects in Australia that meet I/E and population criteria
Thailand	Subjects in Thailand that meet I/E and population criteria
Singapore	Subjects in Singapore that meet I/E and population criteria
Malaysia	Subjects in Malaysia that meet I/E and population criteria
Indonesia	Subjects in Indonesia that meet I/E and population criteria
Russia	Subjects in Russia that meet I/E and population criteria

Measured Values

	China	Taiwan	South Korea	Australia	Thailand	Singapore	Malaysia	Indonesia	Russia
Number of Participants Analyzed [units:participants]	1391	271	62	58	87	100	49	273	924
Overall Tumour Epidermal Growth Factor Receptor (EGFR) Mutation Status [units: Percentage of participants] Number (95% Confidence Interval)
Mutation Negative	59.2 (56.6 to 61.8)	52.0 (45.9 to 58.1)	77.4 (65.0 to 87.1)	70.7 (57.3 to 81.9)	71.3 (60.6 to 80.5)	45.0 (35.0 to 55.3)	65.3 (50.4 to 78.3)	57.5 (51.4 to 63.4)	88.1 (85.8 to 90.1)
Mutation Positive	40.8 (38.2 to 43.4)	48.0 (41.9 to 54.1)	22.6 (12.9 to 35.0)	29.3 (18.1 to 42.7)	28.7 (19.5 to 39.4)	55.0 (44.7 to 65.0)	34.7 (21.7 to 49.6)	42.5 (36.6 to 48.6)	11.9 (9.9 to 14.2)

No statistical analysis provided for Overall Tumour Epidermal Growth Factor Receptor (EGFR) Mutation Status

2. Primary Outcome Measure: Tumour EGFR Mutation by Subtype [ Time Frame: At Screening ]

Measure Type	Primary
Measure Name	Tumour EGFR Mutation by Subtype
Measure Description	Frequency distribution of subjects with a positive mutation status by the mutation subtype and country.
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Tumour Evaluable Population

Reporting Groups

	Description
China	Subjects in China that meet I/E and population criteria.
Taiwan	Subjects in Taiwan that meet I/E and population criteria
South Korea	Subjects in South Korea that meet I/E and population criteria
Australia	Subjects in Australia that meet I/E and population criteria
Thailand	Subjects in Thailand that meet I/E and population criteria
Singapore	Subjects in Singapore that meet I/E and population criteria
Malaysia	Subjects in Malaysia that meet I/E and population criteria
Indonesia	Subjects in Indonesia that meet I/E and population criteria
Russia	Subjects in Russia that meet I/E and population criteria

Measured Values

	China	Taiwan	South Korea	Australia	Thailand	Singapore	Malaysia	Indonesia	Russia
Number of Participants Analyzed [units:participants]	1391	271	62	58	87	100	49	273	924
Tumour EGFR Mutation by Subtype [units: Participants]
G719x mutation only	8	1	0	0	2	0	0	0	0
Exon 19 deletion only	283	61	5	12	13	27	7	43	63
Exon 19 deletion +T790M	0	1	0	0	0	0	0	0	0
Exon 19 deletion + other	6	1	0	0	0	5	0	0	8
Exon 19 Other only	2	0	0	0	0	0	0	0	0
T790M only	0	2	0	0	0	0	0	0	0
T790M + other	2	0	0	0	0	0	0	0	0
Exon 20 insertions only	11	2	1	0	2	3	2	0	0
L858R mutation only	239	57	7	4	7	17	8	70	26
S768I mutation only	0	1	1	0	0	0	0	0	1
L858R mutation + other	1	0	0	0	0	0	0	0	2
L861Q mutation only	6	3	0	0	0	0	0	3	2
Exon 21 Other only	3	0	0	1	0	0	0	0	6
Other	6	1	0	0	1	3	0	0	2

No statistical analysis provided for Tumour EGFR Mutation by Subtype

3. Primary Outcome Measure: Tumour EGFR Mutation Status by Histology [ Time Frame: At Screening ]

Measure Type	Primary
Measure Name	Tumour EGFR Mutation Status by Histology
Measure Description	Only subjects who had a recorded Histological Type of Adenocarcinoma or Non-adenocarcinoma are included. Confidence intervals were calculated using Clopper Pearson method for each country.
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Tumour Evaluable Population

Reporting Groups

	Description
China-Adenocarcinoma	Subjects in China that meet I/E and population criteria with a histological type of Adenocarcinoma.
China-Non-adenocarcinoma	Subjects in China that meet I/E and population criteria with a histological type of Non-Adenocarcinoma.
Taiwan-Adenocarcinoma	Subjects in Taiwan that meet I/E and population criteria with a histological type of Adenocarcinoma.
Taiwan-Non-adenocarcinoma	Subjects in Taiwan that meet I/E and population criteria with a histological type of Non-Adenocarcinoma.
South Korea-Adenocarcinoma	Subjects in South Korea that meet I/E and population criteria with a histological type of Adenocarcinoma.
South Korea-Non-adenocarcinoma	Subjects in South Korea that meet I/E and population criteria with a histological type of Non-Adenocarcinoma.
Australia-Adenocarcinoma	Subjects in Australia that meet I/E and population criteria with a histological type of Adenocarcinoma.
Australia-Non-adenocarcinoma	Subjects in Australia that meet I/E and population criteria with a histological type of Non-Adenocarcinoma.
Thailand-Adenocarcinoma	Subjects in Thailand that meet I/E and population criteria with a histological type of Adenocarcinoma.
Thailand-Non-adenocarcinoma	Subjects in Thailand that meet I/E and population criteria with a histological type of Non-Adenocarcinoma.
Singapore-Adenocarcinoma	Subjects in Singapore that meet I/E and population criteria with a histological type of Adenocarcinoma.
Singapore-Non-adenocarcinoma	Subjects in Singapore that meet I/E and population criteria with a histological type of Non-Adenocarcinoma.
Malaysia-Adenocarcinoma	Subjects in Malaysia that meet I/E and population criteria with a histological type of Adenocarcinoma.
Malaysia-Non-adenocarcinoma	Subjects in Malaysia that meet I/E and population criteria with a histological type of Non-Adenocarcinoma.
Indonesia-Adenocarcinoma	Subjects in Indonesia that meet I/E and population criteria with a histological type of Adenocarcinoma.
Indonesia-Non-adenocarcinoma	Subjects in Indonesia that meet I/E and population criteria with a histological type of Non-Adenocarcinoma.
Russia-Adenocarcinoma	Subjects in Russia that meet I/E and population criteria with a histological type of Adenocarcinoma.
Russia-Non-adenocarcinoma	Subjects in Russia that meet I/E and population criteria with a histological type of Non-Adenocarcinoma.

Measured Values

	China-Adenocarcinoma	China-Non-adenocarcinoma	Taiwan-Adenocarcinoma	Taiwan-Non-adenocarcinoma	South Korea-Adenocarcinoma	South Korea-Non-adenocarcinoma	Australia-Adenocarcinoma	Australia-Non-adenocarcinoma	Thailand-Adenocarcinoma	Thailand-Non-adenocarcinoma	Singapore-Adenocarcinoma	Singapore-Non-adenocarcinoma	Malaysia-Adenocarcinoma	Malaysia-Non-adenocarcinoma	Indonesia-Adenocarcinoma	Indonesia-Non-adenocarcinoma	Russia-Adenocarcinoma	Russia-Non-adenocarcinoma
Number of Participants Analyzed [units:participants]	1026	361	208	61	46	15	49	7	73	13	95	3	40	6	212	59	500	402
Tumour EGFR Mutation Status by Histology [units: Percentage of participants] Number (95% Confidence Interval)
Mutation Negative	48.7 (45.6 to 51.8)	88.9 (85.2 to 92.0)	42.8 (36.0 to 49.8)	83.6 (71.9 to 91.8)	69.6 (54.2 to 82.3)	100.0 (78.2 to 100.0)	67.3 (52.5 to 80.1)	85.7 (42.1 to 99.6)	69.9 (58.0 to 80.1)	84.6 (54.6 to 98.1)	43.2 (33.0 to 53.7)	66.7 (9.4 to 99.2)	62.5 (45.8 to 77.3)	83.3 (35.9 to 99.6)	54.7 (47.8 to 61.5)	67.8 (54.4 to 79.4)	82.0 (78.3 to 85.3)	96.3 (93.9 to 97.9)
Mutation Positive	51.3 (48.2 to 54.4)	11.1 (8.0 to 14.8)	57.2 (50.2 to 64.0)	16.4 (8.2 to 28.1)	30.4 (17.7 to 45.8)	0.0 (0.0 to 21.8)	32.7 (19.9 to 47.5)	14.3 (0.4 to 57.9)	30.1 (19.9 to 42.0)	15.4 (1.9 to 45.4)	56.8 (46.3 to 67.0)	33.3 (0.8 to 90.6)	37.5 (22.7 to 54.2)	16.7 (0.4 to 64.1)	45.3 (38.5 to 52.2)	32.2 (20.6 to 45.6)	18.0 (14.7 to 21.7)	3.7 (2.1 to 6.1)

No statistical analysis provided for Tumour EGFR Mutation Status by Histology

4. Primary Outcome Measure: Overall Plasma EGFR Mutation Status [ Time Frame: At Screening ]

Measure Type	Primary
Measure Name	Overall Plasma EGFR Mutation Status
Measure Description	Plasma samples were only performed in China, Taiwan, South Korea and Russia. The Confidence intervals were calculated using Clopper Pearson method for each country.
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Plasma Evaluable Population

Reporting Groups

	Description
China	Subjects in China that meet I/E and population criteria.
Taiwan	Subjects in Taiwan that meet I/E and population criteria
South Korea	Subjects in South Korea that meet I/E and population criteria
Russia	Subjects in Russia that meet I/E and population criteria

Measured Values

	China	Taiwan	South Korea	Russia
Number of Participants Analyzed [units:participants]	1421	271	61	941
Overall Plasma EGFR Mutation Status [units: Percentage of participants] Number (95% Confidence Interval)
Mutation Negative	79.3 (77.1 to 81.4)	73.1 (67.4 to 78.3)	86.9 (75.8 to 94.2)	90.8 (88.7 to 92.5)
Mutation Positive	20.7 (18.6 to 22.9)	26.9 (21.7 to 32.6)	13.1 (5.8 to 24.2)	9.2 (7.5 to 11.3)

No statistical analysis provided for Overall Plasma EGFR Mutation Status

5. Primary Outcome Measure: Plasma EGFR Mutation by Subtype [ Time Frame: At Screening ]

Measure Type	Primary
Measure Name	Plasma EGFR Mutation by Subtype
Measure Description	Plasma samples were only performed in China, Taiwan, South Korea and Russia. Frequency distribution of subjects with a positive mutation status by the mutation subtype and country.
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Plasma Evaluable Population

Reporting Groups

	Description
China	Subjects in China that meet I/E and population criteria.
Taiwan	Subjects in Taiwan that meet I/E and population criteria
South Korea	Subjects in South Korea that meet I/E and population criteria
Russia	Subjects in Russia that meet I/E and population criteria

Measured Values

	China	Taiwan	South Korea	Russia
Number of Participants Analyzed [units:participants]	1421	271	61	941
Plasma EGFR Mutation by Subtype [units: Participants]
G719X mutation only	5	0	0	0
Exon 19 deletion only	152	35	1	61
Exon 19 deletion + other	0	1	0	0
T790M + other	2	0	0	0
Exon 20 insertions only	4	2	0	1
L858R mutation only	122	30	6	25
S768I mutation only	2	1	0	0
L858R mutation + Other	0	1	0	0
L861Q mutation only	4	1	0	0
Other	3	2	1	0

No statistical analysis provided for Plasma EGFR Mutation by Subtype

6. Primary Outcome Measure: Plasma EGFR Mutation Status by Histology [ Time Frame: At Screening ]

Measure Type	Primary
Measure Name	Plasma EGFR Mutation Status by Histology
Measure Description	Only subjects who had a recorded Histological Type of Adenocarcinoma or Non-adenocarcinoma are included. Confidence intervals were calculated using Clopper Pearson method for each country
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Plasma Evaluable Population

Reporting Groups

	Description
China-Adenocarcinoma	Subjects in China that meet I/E and population criteria with a histological type of Adenocarcinoma.
China-Non-Adenocarcinoma	Subjects in China that meet I/E and population criteria with a histological type of Non-Adenocarcinoma.
Taiwan-Adenocarcinoma	Subjects in Taiwan that meet I/E and population criteria with a histological type of Adenocarcinoma.
Taiwan-Non-adenocarcinoma	Subjects in Taiwan that meet I/E and population criteria with a histological type of Non-Adenocarcinoma.
South Korea-Adenocarcinoma	Subjects in South Korea that meet I/E and population criteria with a histological type of Adenocarcinoma.
South Korea-Non-adenocarcinoma	Subjects in South Korea that meet I/E and population criteria with a histological type of Non-Adenocarcinoma.
Russia-Adenocarcinoma	Subjects in Russia that meet I/E and population criteria with a histological type of Adenocarcinoma.
Russia-Non-adenocarcinoma	Subjects in Russia that meet I/E and population criteria with a histological type of Non-Adenocarcinoma.

Measured Values

	China-Adenocarcinoma	China-Non-Adenocarcinoma	Taiwan-Adenocarcinoma	Taiwan-Non-adenocarcinoma	South Korea-Adenocarcinoma	South Korea-Non-adenocarcinoma	Russia-Adenocarcinoma	Russia-Non-adenocarcinoma
Number of Participants Analyzed [units:participants]	1047	369	208	61	46	15	513	409
Plasma EGFR Mutation Status by Histology [units: Percentage of participants] Number (95% Confidence Interval)
Mutation Negative	74.4 (71.6 to 77.0)	93.2 (90.2 to 95.6)	68.3 (61.5 to 74.5)	90.2 (79.8 to 96.3)	82.6 (68.6 to 92.2)	100.0 (78.2 to 100.0)	89.3 (86.3 to 91.8)	92.9 (90.0 to 95.2)
Mutation Positive	25.6 (23.0 to 28.4)	6.8 (4.4 to 9.8)	31.7 (25.5 to 38.5)	9.8 (3.7 to 20.2)	17.4 (7.8 to 31.4)	0.0 (0.0 to 21.8)	10.7 (8.2 to 13.7)	7.1 (4.8 to 10.0)

No statistical analysis provided for Plasma EGFR Mutation Status by Histology

7. Secondary Outcome Measure: Concordance Rate of Comparison of Mutation Status Between Tumour and Plasma Samples [ Time Frame: At Screening ]

Measure Type	Secondary
Measure Name	Concordance Rate of Comparison of Mutation Status Between Tumour and Plasma Samples
Measure Description	Plasma samples were only performed in China, Taiwan, South Korea and Russia.
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Tumour and Plasma Evaluable Population

Reporting Groups

	Description
China	Subjects in China that meet I/E and population criteria.
Taiwan	Subjects in Taiwan that meet I/E and population criteria
South Korea	Subjects in South Korea that meet I/E and population criteria
Russia	Subjects in Russia that meet I/E and population criteria

Measured Values

	China	Taiwan	South Korea	Russia
Number of Participants Analyzed [units:participants]	1355	271	61	894
Concordance Rate of Comparison of Mutation Status Between Tumour and Plasma Samples [units: Percentage]	77.6	76.8	83.6	85.8

No statistical analysis provided for Concordance Rate of Comparison of Mutation Status Between Tumour and Plasma Samples

8. Secondary Outcome Measure: Sensitivity and Specificity of Comparison of Mutation Status Between Tumour and Plasma Samples [ Time Frame: At Screening ]

Measure Type	Secondary
Measure Name	Sensitivity and Specificity of Comparison of Mutation Status Between Tumour and Plasma Samples
Measure Description	Plasma samples were only performed in China, Taiwan, South Korea, and Russia. Participants only include those who had sensitivity and specificity tests performed.
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Tumour and Plasma Evaluable Population

Reporting Groups

	Description
China - Sensitivity	Subjects in China that meet I/E and population criteria, who had a sensitivity test performed.
China - Specificty	Subjects in China that meet I/E and population criteria, who had a specificity test performed.
Taiwan - Sensitivity	Subjects in Taiwan that meet I/E and population criteria, who had a sensitivity test performed.
Taiwan - Specificity	Subjects in Taiwan that meet I/E and population criteria, who had a specificity test performed.
South Korea - Sensitivity	Subjects in South Korea that meet I/E and population criteria, who had a sensitivity test performed.
South Korea - Specificity	Subjects in South Korea that meet I/E and population criteria, who had a specificity test performed.
Russia - Sensitivity	Subjects in Russia that meet I/E and population criteria, who had a sensitivity test performed.
Russia - Specificity	Subjects in Russia that meet I/E and population criteria, who had a specificity test performed.

Measured Values

	China - Sensitivity	China - Specificty	Taiwan - Sensitivity	Taiwan - Specificity	South Korea - Sensitivity	South Korea - Specificity	Russia - Sensitivity	Russia - Specificity
Number of Participants Analyzed [units:participants]	548	807	130	141	14	47	109	785
Sensitivity and Specificity of Comparison of Mutation Status Between Tumour and Plasma Samples [units: Percentage]	48.7	97.1	53.8	97.9	42.9	95.7	30.3	93.5

No statistical analysis provided for Sensitivity and Specificity of Comparison of Mutation Status Between Tumour and Plasma Samples

9. Secondary Outcome Measure: Predictive Values of Comparison of Mutation Status Between Tumour and Plasma Samples [ Time Frame: At Screening ]

Measure Type	Secondary
Measure Name	Predictive Values of Comparison of Mutation Status Between Tumour and Plasma Samples
Measure Description	Plasma samples were only performed in China, Taiwan, South Korea, and Russia. Participants include only those who had Positive and Negative Predictive tests performed.
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Tumour and Plasma Evaluable Population

Reporting Groups

	Description
China - Positive Predictive Value	Subjects in China that meet I/E and population criteria, who had a Positive Predictive test performed.
China - Negative Predictive Value	Subjects in China that meet I/E and population criteria, who had a Negative Predictive test performed.
Taiwan - Positive Predictive Value	Subjects in Taiwan that meet I/E and population criteria, who had a Positive Predictive test performed.
Taiwan - Negative Predictive Value	Subjects in Taiwan that meet I/E and population criteria, who had a Negative Predictive test performed.
South Korea - Positive Predictive Value	Subjects in South Korea that meet I/E and population criteria, who had a Positive Predictive test performed.
South Korea - Negative Predictive Value	Subjects in South Korea that meet I/E and population criteria, who had a Negative Predictive test performed.
Russia - Positive Predictive Value	Subjects in Russia that meet I/E and population criteria, who had a Positive Predictive test performed.
Russia - Negative Predictive Value	Subjects in Russia that meet I/E and population criteria, who had a Negative Predictive test performed.

Measured Values

	China - Positive Predictive Value	China - Negative Predictive Value	Taiwan - Positive Predictive Value	Taiwan - Negative Predictive Value	South Korea - Positive Predictive Value	South Korea - Negative Predictive Value	Russia - Positive Predictive Value	Russia - Negative Predictive Value
Number of Participants Analyzed [units:participants]	290	1065	73	198	8	53	84	810
Predictive Values of Comparison of Mutation Status Between Tumour and Plasma Samples [units: Percentage]	92.1	73.6	95.9	69.7	75.0	84.9	39.3	90.6

No statistical analysis provided for Predictive Values of Comparison of Mutation Status Between Tumour and Plasma Samples

10. Secondary Outcome Measure: Tumour EGFR Mutation Testing [ Time Frame: At Screening ]

Measure Type	Secondary
Measure Name	Tumour EGFR Mutation Testing
Measure Description	Frequencies of tumour EGFR mutation testing practices parameters.
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Enrolled Population

Reporting Groups

	Description
China	Subjects in China that meet I/E and population criteria.
Taiwan	Subjects in Taiwan that meet I/E and population criteria
South Korea	Subjects in South Korea that meet I/E and population criteria
Australia	Subjects in Australia that meet I/E and population criteria
Thailand	Subjects in Thailand that meet I/E and population criteria
Singapore	Subjects in Singapore that meet I/E and population criteria
Malaysia	Subjects in Malaysia that meet I/E and population criteria
Indonesia	Subjects in Indonesia that meet I/E and population criteria
Russia	Subjects in Russia that meet I/E and population criteria

Measured Values

	China	Taiwan	South Korea	Australia	Thailand	Singapore	Malaysia	Indonesia	Russia
Number of Participants Analyzed [units:participants]	1458	271	62	71	94	102	50	302	972
Tumour EGFR Mutation Testing [units: Participants]
Tumour Sample	1394	271	62	60	92	101	49	273	936
Mutation Test Not Performed	64	0	0	11	2	1	1	29	36

No statistical analysis provided for Tumour EGFR Mutation Testing

11. Secondary Outcome Measure: Tumour EGFR Mutation Testing Rates [ Time Frame: At Screening ]

Measure Type	Secondary
Measure Name	Tumour EGFR Mutation Testing Rates
Measure Description	Testing Success rate is the percentage of subjects with a non-missing test result. Mutation Detection Rate is the percentage of subjects with successful test that detects a mutation.
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Enrolled Population

Reporting Groups

	Description
China	Subjects in China that meet I/E and population criteria.
Taiwan	Subjects in Taiwan that meet I/E and population criteria
South Korea	Subjects in South Korea that meet I/E and population criteria
Australia	Subjects in Australia that meet I/E and population criteria
Thailand	Subjects in Thailand that meet I/E and population criteria
Singapore	Subjects in Singapore that meet I/E and population criteria
Malaysia	Subjects in Malaysia that meet I/E and population criteria
Indonesia	Subjects in Indonesia that meet I/E and population criteria
Russia	Subjects in Russia that meet I/E and population criteria

Measured Values

	China	Taiwan	South Korea	Australia	Thailand	Singapore	Malaysia	Indonesia	Russia
Number of Participants Analyzed [units:participants]	1458	271	62	71	94	102	50	302	972
Tumour EGFR Mutation Testing Rates [units: Percentage of Participants]
Testing Success Rate	99.8	100.0	100.0	96.7	94.6	99.0	100.0	100.0	98.7
Mutation Detection Rate	40.7	48.0	24.2	28.3	27.2	54.5	34.7	42.5	12.7

No statistical analysis provided for Tumour EGFR Mutation Testing Rates

12. Secondary Outcome Measure: Tumour EGFR Mutation Testing Turnaround Time [ Time Frame: At Screening ]

Measure Type	Secondary
Measure Name	Tumour EGFR Mutation Testing Turnaround Time
Measure Description	Tumour EGFR mutation testing turnaround time is the number of days from the test request to getting the test result.
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Enrolled Population

Reporting Groups

	Description
China	Subjects in China that meet I/E and population criteria.
Taiwan	Subjects in Taiwan that meet I/E and population criteria
South Korea	Subjects in South Korea that meet I/E and population criteria
Australia	Subjects in Australia that meet I/E and population criteria
Thailand	Subjects in Thailand that meet I/E and population criteria
Singapore	Subjects in Singapore that meet I/E and population criteria
Malaysia	Subjects in Malaysia that meet I/E and population criteria
Indonesia	Subjects in Indonesia that meet I/E and population criteria
Russia	Subjects in Russia that meet I/E and population criteria

Measured Values

	China	Taiwan	South Korea	Australia	Thailand	Singapore	Malaysia	Indonesia	Russia
Number of Participants Analyzed [units:participants]	1458	271	62	71	94	102	50	302	972
Tumour EGFR Mutation Testing Turnaround Time [units: Time (Days)] Mean (Standard Deviation)	6.2 (5.34)	7.4 (12.29)	11.7 (12.70)	12.9 (8.19)	70.8 (43.85)	8.4 (4.90)	8.6 (3.55)	6.5 (2.33)	14.3 (26.84)

No statistical analysis provided for Tumour EGFR Mutation Testing Turnaround Time

13. Secondary Outcome Measure: Plasma EGFR Mutation Testing [ Time Frame: At Screening ]

Measure Type	Secondary
Measure Name	Plasma EGFR Mutation Testing
Measure Description	Plasma samples were only performed in China, Taiwan, South Korea and Russia. Frequencies of plasma EGFR mutation testing practices parameters.
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Enrolled Population

Reporting Groups

	Description
China	Subjects in China that meet I/E and population criteria.
Taiwan	Subjects in Taiwan that meet I/E and population criteria
South Korea	Subjects in South Korea that meet I/E and population criteria
Russia	Subjects in Russia that meet I/E and population criteria

Measured Values

	China	Taiwan	South Korea	Russia
Number of Participants Analyzed [units:participants]	1458	271	62	972
Plasma EGFR Mutation Testing [units: Participants]
Plasma Sample	1421	271	62	950
Mutation Test Not performed	37	0	0	22

No statistical analysis provided for Plasma EGFR Mutation Testing

14. Secondary Outcome Measure: Plasma EGFR Mutation Testing Rates [ Time Frame: At Screening ]

Measure Type	Secondary
Measure Name	Plasma EGFR Mutation Testing Rates
Measure Description	Testing Success rate is the percentage of subjects with a non-missing test result. Mutation Detection Rate is the percentage of subjects with successful test that detects a mutation. Plasma samples were only performed in China, Taiwan, South Korea and Russia.
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Enrolled Population

Reporting Groups

	Description
China	Subjects in China that meet I/E and population criteria.
Taiwan	Subjects in Taiwan that meet I/E and population criteria
South Korea	Subjects in South Korea that meet I/E and population criteria
Russia	Subjects in Russia that meet I/E and population criteria

Measured Values

	China	Taiwan	South Korea	Russia
Number of Participants Analyzed [units:participants]	1458	271	62	972
Plasma EGFR Mutation Testing Rates [units: Percentage of Participants]
Testing Success Rate	100.0	100.0	98.4	99.1
Mutation Detection Rate	20.7	26.9	12.9	9.2

No statistical analysis provided for Plasma EGFR Mutation Testing Rates

15. Secondary Outcome Measure: Plasma EGFR Mutation Testing Turnaround Time [ Time Frame: At Screening ]

Measure Type	Secondary
Measure Name	Plasma EGFR Mutation Testing Turnaround Time
Measure Description	Plasma samples were only performed in China, Taiwan, South Korea and Russia. Plasma EGFR mutation testing turnaround time is the number of days from the test request to getting the test result.
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Enrolled Population

Reporting Groups

	Description
China	Subjects in China that meet I/E and population criteria
Taiwan	Subjects in Taiwan that meet I/E and population criteria
South Korea	Subjects in South Korea that meet I/E and population criteria
Russia	Subjects in Russia that meet I/E and population criteria

Measured Values

	China	Taiwan	South Korea	Russia
Number of Participants Analyzed [units:participants]	1458	271	62	972
Plasma EGFR Mutation Testing Turnaround Time [units: Time (Days)] Mean (Standard Deviation)	39.8 (44.24)	26.7 (12.62)	18.1 (13.72)	90.1 (105.69)

No statistical analysis provided for Plasma EGFR Mutation Testing Turnaround Time

16. Secondary Outcome Measure: Demographics and Disease Characteristics by Tumour EGFR Mutation status [ Time Frame: At Screening ]

Measure Type	Secondary
Measure Name	Demographics and Disease Characteristics by Tumour EGFR Mutation status
Measure Description	Correlation of demographic and disease characteristics are summarized by EGFR mutation status with results from a multivariate logistic regression using stepwise forward selection with a 10% significance level for model entry.
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Tumour Evaluable Population

Reporting Groups

	Description
EGFR Mutation Positive	Participants who were EGFR Mutation Positive for the analysis population.
EGFR Mutation Negative	Participants who were EGFR Mutation Negative for the analysis population.

Measured Values

	EGFR Mutation Positive	EGFR Mutation Negative
Number of Participants Analyzed [units:participants]	1051	2164
Demographics and Disease Characteristics by Tumour EGFR Mutation status [units: Participants]
Histology: Adenocarcinoma	952	1297
Histology: Non-adenocarcinoma	89	838
Smoking Status: Never-Smoker	705	647
Smoking Status: Ever-Smoker	346	1517
Gender: Male	480	1647
Gender: Female	571	517
Region: Asia Pacific	941	1350
Region: Russia	110	814
Age: <=65	695	1447
>65	356	717
World Health Organization Performance Status: 0-1	866	1808
World Health Organization Performance Status: 2	128	276
Current Disease Status: IIIA	42	266
Current Disease Status: IIIB	86	371
Current Disease Status: IV	923	1527
Number of Organs with Metastasis = 1	458	901
Number of Organs with Metastasis = 2	266	408
Number of Organs with Metastasis = 3	127	149
Number of Organs with Metastasis = 4	53	61
Number of Organs with Metastasis = 5	16	15
Number of Organs with Metastasis = 6	2	2
Number of Organs with Metastasis = 7	3	1

Statistical Analysis 1 for Demographics and Disease Characteristics by Tumour EGFR Mutation status

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Regression stepwise]
P-Value^[4]	0.0001
Other^[5]	81.1237

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	10% significance level for entry criteria
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Histology: Adenocarcinoma vs Non-adenocarcinoma
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Demographics and Disease Characteristics by Tumour EGFR Mutation status

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Regression stepwise]
P-Value^[4]	0.0001
Odds Ratio (OR)^[5]	3.973

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	10% significance level for model entry
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Histology: Adenocarcinoma vs Non-adenocarcinoma
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Demographics and Disease Characteristics by Tumour EGFR Mutation status

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Regression Stepwise]
P-Value^[4]	0.0075
Other^[5]	7.1526

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	10% significance level for entry criteria
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Gender: Male vs. Female
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Demographics and Disease Characteristics by Tumour EGFR Mutation status

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Regression Stepwise]
P-Value^[4]	0.0075
Odds Ratio (OR)^[5]	1.409

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	10% Significance Level for model entry
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Gender: Male vs. Female
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 5 for Demographics and Disease Characteristics by Tumour EGFR Mutation status

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Regression Stepwise]
P-Value^[4]	0.0001
Other^[5]	51.8456

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	10% significance level for entry criteria
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Smoking Status: Never-smoker vs. Ever-smoker
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 6 for Demographics and Disease Characteristics by Tumour EGFR Mutation status

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Regression Stepwise]
P-Value^[4]	0.0001
Odds Ratio (OR)^[5]	2.515

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	10% Significance Level for model entry
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Smoking Status: Never-smoker vs. Ever-smoker
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 7 for Demographics and Disease Characteristics by Tumour EGFR Mutation status

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Regression Stepwise]
P-Value^[4]	0.0001
Other^[5]	98.1065

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	10% Significance Level for entry criteria
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Region: Asia Pacific vs. Russia
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 8 for Demographics and Disease Characteristics by Tumour EGFR Mutation status

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Regression Stepwise]
P-Value^[4]	0.0001
Odds Ratio (OR)^[5]	3.929

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	10% Significance Level for model entry
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Region: Asia Pacific vs. Russia
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 9 for Demographics and Disease Characteristics by Tumour EGFR Mutation status

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Regression Stepwise]
P-Value^[4]	0.0909
Other^[5]	2.8589

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	10% significance level for entry criteria
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Number of organs with metastasis
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 10 for Demographics and Disease Characteristics by Tumour EGFR Mutation status

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Regression Stepwise]
P-Value^[4]	0.0909
Odds Ratio (OR)^[5]	1.086

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	10% significance level for model entry
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Number of organs with metastasis
[5]	Other relevant estimation information:
	No text entered.

17. Secondary Outcome Measure: Time Since First Non-small-cell lung carcinoma (NSCLC) Diagnosis by Tumor EGFR Mutation [ Time Frame: At Screening ]

Measure Type	Secondary
Measure Name	Time Since First Non-small-cell lung carcinoma (NSCLC) Diagnosis by Tumor EGFR Mutation
Measure Description	Number of months since the first diagnosis of NSCLC from informed consent date.
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Tumour Evaluable Population

Reporting Groups

	Description
EGFR Mutation Positive	Participants who were EGFR Mutation Positive for the analysis population.
EGFR Mutation Negative	Participants who were EGFR Mutation Negative for the analysis population.

Measured Values

	EGFR Mutation Positive	EGFR Mutation Negative
Number of Participants Analyzed [units:participants]	1051	2164
Time Since First Non-small-cell lung carcinoma (NSCLC) Diagnosis by Tumor EGFR Mutation [units: Months] Mean (Standard Deviation)	2.6 (8.93)	2.6 (9.79)

No statistical analysis provided for Time Since First Non-small-cell lung carcinoma (NSCLC) Diagnosis by Tumor EGFR Mutation

18. Secondary Outcome Measure: Number of Organs with Metastasis by Tumour EGFR Mutation Status [ Time Frame: At Screening ]

Measure Type	Secondary
Measure Name	Number of Organs with Metastasis by Tumour EGFR Mutation Status
Measure Description	Summary of number of organs with metastasis. Only participants with at least 1 organ with metastasis are included.
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Tumour Evaluable Population

Reporting Groups

	Description
EGFR Mutation Positive	Participants who were EGFR Mutation Positive for the analysis population.
EGFR Mutation Negative	Participants who were EGFR Mutation Negative for the analysis population.

Measured Values

	EGFR Mutation Positive	EGFR Mutation Negative
Number of Participants Analyzed [units:participants]	925	1537
Number of Organs with Metastasis by Tumour EGFR Mutation Status [units: Number] Mean (Standard Deviation)	1.8 (1.05)	1.6 (0.91)

No statistical analysis provided for Number of Organs with Metastasis by Tumour EGFR Mutation Status

19. Secondary Outcome Measure: Demographics and Disease Characteristics by Plasma EGFR Mutation status [ Time Frame: At Screening ]

Measure Type	Secondary
Measure Name	Demographics and Disease Characteristics by Plasma EGFR Mutation status
Measure Description	Correlation of demographic and disease characteristics are summarized by EGFR mutation status with results from a multivariate logistic regression using stepwise forward selection with a 10% significance level for model entry.
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Plasma Evaluable Population

Reporting Groups

	Description
EGFR Mutation Positive	Participants who were EGFR Mutation Positive for the analysis population.
EGFR Mutation Negative	Participants who were EGFR Mutation Negative for the analysis population.

Measured Values

	EGFR Mutation Positive	EGFR Mutation Negative
Number of Participants Analyzed [units:participants]	462	2232
Demographics and Disease Characteristics by Plasma EGFR Mutation status [units: Participants]
Histology: Adenocarcinoma	397	1417
Histology: Non-adenocarcinoma	60	794
Smoking Status: Never-Smoker	298	835
Smoking Status: Ever-Smoker	164	1397
Gender: Male	228	1575
Gender: Female	234	657
Region: Asia Pacific	375	1378
Region: Russia	87	854
Age: <=65	337	1454
Age: >65	125	778
WHO Performance Status: 0-1	400	1956
WHO Performance Status: 2	43	237
Current Disease Status: IIIA	23	257
Current Disease Status: IIIB	32	378
Current Disease Status: IV	407	1597
Number of Organs with Metastasis = 1	167	956
Number of Organs with Metastasis = 2	120	420
Number of Organs with Metastasis = 3	67	155
Number of Organs with Metastasis = 4	37	57
Number of Organs with Metastasis = 5	12	17
Number of Organs with Metastasis = 6	2	2
Number of Organs with Metastasis = 7	3	0

Statistical Analysis 1 for Demographics and Disease Characteristics by Plasma EGFR Mutation status

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Regression Stepwise]
P-Value^[4]	0.0009
Other^[5]	11.1060

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	10% Significance Level for entry criteria
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Age: <=65 vs. >65
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Demographics and Disease Characteristics by Plasma EGFR Mutation status

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Regression Stepwise]
P-Value^[4]	0.0009
Odds Ratio (OR)^[5]	1.561

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	10% Significance Level for model entry
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Age: <=65 vs. >65
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Demographics and Disease Characteristics by Plasma EGFR Mutation status

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Regression Stepwise]
P-Value^[4]	0.0001
Other^[5]	34.1075

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	10% Significance Level for entry criteria
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Number of Organs with Metastisis
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Demographics and Disease Characteristics by Plasma EGFR Mutation status

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Regression Stepwise]
P-Value^[4]	0.0001
Odds Ratio (OR)^[5]	1.386

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	10% significance level for model entry
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Number of Organs with Metastisis
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 5 for Demographics and Disease Characteristics by Plasma EGFR Mutation status

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Regression Stepwise]
P-Value^[4]	0.0002
Other^[5]	14.0806

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	10% Significance Level for entry criteria
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Histology: Adenocarcinoma vs. Non-adenocarcinoma
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 6 for Demographics and Disease Characteristics by Plasma EGFR Mutation status

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Regression Stepwise]
P-Value^[4]	0.0002
Odds Ratio (OR)^[5]	1.955

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	10% Significance Level for model entry
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Histology: Adenocarcinoma vs. Non-adenocarcinoma
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 7 for Demographics and Disease Characteristics by Plasma EGFR Mutation status

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Regression Stepwise]
P-Value^[4]	0.0001
Other^[5]	33.8574

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	10% Significance Level for entry criteria
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Smoking Status: Never-smoker vs. Ever-smoker
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 8 for Demographics and Disease Characteristics by Plasma EGFR Mutation status

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Regression Stepwise]
P-Value^[4]	0.0001
Odds Ratio (OR)^[5]	2.077

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	10% Significance Level for model entry
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Smoking Status: Never-smoker vs. Ever-smoker
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 9 for Demographics and Disease Characteristics by Plasma EGFR Mutation status

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Regression Stepwise]
P-Value^[4]	0.0001
Other^[5]	21.2537

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	10% Significance Level for entry criteria
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Region: Asia Pacific vs. Russia
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 10 for Demographics and Disease Characteristics by Plasma EGFR Mutation status

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Regression Stepwise]
P-Value^[4]	0.0001
Odds Ratio (OR)^[5]	2.084

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	10% Significance Level for model entry
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Region: Asia Pacific vs. Russia
[5]	Other relevant estimation information:
	No text entered.

20. Secondary Outcome Measure: Time Since First NSCLC Diagnosis by Plasma EGFR Mutation [ Time Frame: At Screening ]

Measure Type	Secondary
Measure Name	Time Since First NSCLC Diagnosis by Plasma EGFR Mutation
Measure Description	Number of months since the first diagnosis of NSCLC from informed consent date.
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Plasma Evaluable Population

Reporting Groups

	Description
EGFR Mutation Positive	Participants who were EGFR Mutation Positive for the analysis population.
EGFR Mutation Negative	Participants who were EGFR Mutation Negative for the analysis population.

Measured Values

	EGFR Mutation Positive	EGFR Mutation Negative
Number of Participants Analyzed [units:participants]	462	2232
Time Since First NSCLC Diagnosis by Plasma EGFR Mutation [units: Months] Mean (Standard Deviation)	2.2 (7.99)	3.0 (11.09)

No statistical analysis provided for Time Since First NSCLC Diagnosis by Plasma EGFR Mutation

21. Secondary Outcome Measure: Number of Organs with Metastasis by Plasma EGFR Mutation Status [ Time Frame: At Screening ]

Measure Type	Secondary
Measure Name	Number of Organs with Metastasis by Plasma EGFR Mutation Status
Measure Description	Summary of number of organs with metastasis. Only participants with at least 1 organ with metastasis are included.
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Plasma Evaluable Population

Reporting Groups

	Description
EGFR Mutation Positive	Participants who were EGFR Mutation Positive for the analysis population.
EGFR Mutation Negative	Participants who were EGFR Mutation Negative for the analysis population.

Measured Values

	EGFR Mutation Positive	EGFR Mutation Negative
Number of Participants Analyzed [units:participants]	408	1607
Number of Organs with Metastasis by Plasma EGFR Mutation Status [units: Number] Mean (Standard Deviation)	2.1 (1.21)	1.6 (0.89)

No statistical analysis provided for Number of Organs with Metastasis by Plasma EGFR Mutation Status

22. Secondary Outcome Measure: First Line Treatment Choice by Asia Pacific Country [ Time Frame: At Screening ]

Measure Type	Secondary
Measure Name	First Line Treatment Choice by Asia Pacific Country
Measure Description
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Tumour Evaluable Population

Reporting Groups

	Description
China	Subjects in China that meet I/E and population criteria.
Taiwan	Subjects in Taiwan that meet I/E and population criteria
South Korea	Subjects in South Korea that meet I/E and population criteria
Australia	Subjects in Australia that meet I/E and population criteria
Thailand	Subjects in Thailand that meet I/E and population criteria
Singapore	Subjects in Singapore that meet I/E and population criteria
Malaysia	Subjects in Malaysia that meet I/E and population criteria
Indonesia	Subjects in Indonesia that meet I/E and population criteria
Russia	Subjects in Russia that meet I/E and population criteria

Measured Values

	China	Taiwan	South Korea	Australia	Thailand	Singapore	Malaysia	Indonesia	Russia
Number of Participants Analyzed [units:participants]	1391	271	62	58	87	100	49	273	924
First Line Treatment Choice by Asia Pacific Country [units: Participants]
Systemic Anticancer Treatment: Yes	1151	218	44	45	65	87	29	174	641
Systemic Anticancer Treatment: No	240	53	18	13	22	13	20	99	283
Afatinib	0	4	1	3	0	10	0	0	13
Bevacizumab	5	0	1	1	0	0	0	0	1
Carboplatin	273	2	10	26	52	23	10	100	235
Cetuximab	0	0	0	0	0	0	0	0	1
Cisplatin	424	11	15	3	7	9	12	0	301
Crizotinib	7	0	0	0	0	3	0	0	3
Docetaxel	77	18	0	0	1	0	0	0	19
Erlotinib	21	46	2	5	0	16	0	0	4
Etoposide	12	0	0	2	3	0	0	11	244
Gefitinib	137	65	6	3	1	21	4	73	33
Gemcitabine	284	14	5	25	9	5	22	1	46
Icotinib	55	0	0	0	0	0	0	0	0
Paclitaxel	133	12	9	4	46	4	0	18	166
Pemetrexed	332	25	9	0	0	25	1	0	28
Vincristine	0	0	0	0	0	0	0	0	3
Vinorelbine	41	22	0	1	0	1	2	0	4
Investigational agent	17	0	2	2	0	2	0	0	0
Other Chemotherapy	142	5	1	1	2	0	0	0	44
Surgery: Yes	8	6	1	0	0	1	1	0	12
Surgery: No	1383	265	61	58	87	99	48	273	912
Radiotherapy: Yes	62	26	14	14	3	11	17	7	72
Radiotherapy: No	1329	245	48	44	84	89	32	266	852
Other: Yes	33	0	0	2	0	0	0	0	8
Other: No	1358	271	62	56	87	100	49	273	916

No statistical analysis provided for First Line Treatment Choice by Asia Pacific Country

23. Secondary Outcome Measure: First Line Treatment Choice by Asia Pacific Country by Tumour EGFR Mutation Status [ Time Frame: At Screening ]

Measure Type	Secondary
Measure Name	First Line Treatment Choice by Asia Pacific Country by Tumour EGFR Mutation Status
Measure Description
Time Frame	At Screening
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Tumour Evaluable Population

Reporting Groups

	Description
China-Mutation Status Positive	Subjects in China that meet I/E and population criteria, who had a Positive Mutation Status.
China-Mutation Status Negative	Subjects in China that meet I/E and population criteria, who had a Negative Mutation Status.
Taiwan-Mutation Status Positive	Subjects in Taiwan that meet I/E and population criteria, who had a Positive Mutation Status.
Taiwan-Mutation Status Negative	Subjects in Taiwan that meet I/E and population criteria, who had a Negative Mutation Status.
South Korea-Mutation Status Positive	Subjects in South Korea that meet I/E and population criteria, who had a Positive Mutation Status.
South Korea-Mutation Status Negative	Subjects in South Korea that meet I/E and population criteria, who had a Negative Mutation Status.
Australia-Mutation Status Positive	Subjects in Australia that meet I/E and population criteria, who had a Positive Mutation Status.
Australia-Mutation Status Negative	Subjects in Australia that meet I/E and population criteria, who had a Negative Mutation Status.
Thailand-Mutation Status Positive	Subjects in Thailand that meet I/E and population criteria, who had a Positive Mutation Status.
Thailand-Mutation Status Negative	Subjects in Thailand that meet I/E and population criteria, who had a Negative Mutation Status.
Singapore-Mutation Status Positive	Subjects in Singapore that meet I/E and population criteria, who had a Positive Mutation Status.
Singapore-Mutation Status Negative	Subjects in Singapore that meet I/E and population criteria, who had a Negative Mutation Status.
Malaysia-Mutation Status Positive	Subjects in Malaysia that meet I/E and population criteria, who had a Positive Mutation Status.
Malaysia-Mutation Status Negative	Subjects in Malaysia that meet I/E and population criteria, who had a Negative Mutation Status.
Indonesia-Mutation Status Positive	Subjects in Indonesia that meet I/E and population criteria, who had a Positive Mutation Status.
Indonesia-Mutation Status Negative	Subjects in Indonesia that meet I/E and population criteria, who had a Negative Mutation Status.
Russia-Mutation Status Positive	Subjects in Russia that meet I/E and population criteria, who had a Positive Mutation Status.
Russia-Mutation Status Negative	Subjects in Russia that meet I/E and population criteria, who had a Negative Mutation Status.

Measured Values

	China-Mutation Status Positive	China-Mutation Status Negative	Taiwan-Mutation Status Positive	Taiwan-Mutation Status Negative	South Korea-Mutation Status Positive	South Korea-Mutation Status Negative	Australia-Mutation Status Positive	Australia-Mutation Status Negative	Thailand-Mutation Status Positive	Thailand-Mutation Status Negative	Singapore-Mutation Status Positive	Singapore-Mutation Status Negative	Malaysia-Mutation Status Positive	Malaysia-Mutation Status Negative	Indonesia-Mutation Status Positive	Indonesia-Mutation Status Negative	Russia-Mutation Status Positive	Russia-Mutation Status Negative
Number of Participants Analyzed [units:participants]	567	824	130	141	14	48	17	41	25	62	55	45	17	32	116	157	110	814
First Line Treatment Choice by Asia Pacific Country by Tumour EGFR Mutation Status [units: Participants]
Systemic Anticancer Treatment? Yes	499	652	122	96	12	32	13	32	19	46	54	33	10	19	80	94	86	555
Systemic Anticancer Treatment? No	68	172	8	45	2	16	4	9	6	16	1	12	7	13	36	63	24	259
Afatinib	0	0	4	0	1	0	3	0	0	0	10	0	0	0	0	0	13	0
Bevacizumab	1	4	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	1
Carboplatin	96	177	0	2	1	9	1	25	16	36	5	18	3	7	8	94	28	207
Cisplatin	123	301	2	9	0	15	0	3	2	5	1	8	3	9	0	0	15	286
Crizotinib	0	7	0	0	0	0	0	0	0	0	0	3	0	0	0	0	0	3
Docetaxel	19	58	3	15	0	0	0	0	1	0	0	0	0	0	0	0	3	16
Erlotinib	17	4	43	3	2	0	5	0	0	0	16	0	0	0	0	0	3	1
Etoposide	1	11	0	0	0	0	0	2	0	3	0	0	0	0	3	8	18	226
Gefitinib	127	10	65	0	6	0	3	0	0	1	21	0	4	0	73	0	24	9
Gemcitabine	61	223	1	13	0	5	1	24	3	6	1	4	6	16	1	0	2	44
Icotinib	50	5	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Paclitaxel	37	96	2	10	0	9	0	4	13	33	2	2	0	0	4	14	18	148
Pemetrexed	139	193	0	25	1	8	0	0	0	0	3	22	0	1	0	0	1	27
Vincristine	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3
Vinorelbine	14	27	3	19	0	0	0	1	0	0	1	0	0	2	0	0	0	4
Investigational Agent	15	2	0	0	2	0	0	2	0	0	0	2	0	0	0	0	0	0
Other Chemotherapy	52	90	1	4	0	1	1	0	0	2	0	0	0	0	0	0	3	41
Cetuximab	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Surgery: Yes	2	6	5	1	0	1	0	0	0	0	0	1	0	1	0	0	2	10
Surgery: No	565	818	125	140	14	47	17	41	25	62	55	44	17	31	116	157	108	804
Radiotherapy: Yes	21	41	2	24	3	11	3	11	2	1	6	5	6	11	2	5	7	65
Radiotherapy: No	546	783	128	117	11	37	14	30	23	61	49	40	11	21	114	152	103	749
Other: Yes	14	19	0	0	0	0	2	0	0	0	0	0	0	0	0	0	1	7
Other: No	553	805	130	141	14	48	15	41	25	62	55	45	17	32	16	157	109	807

No statistical analysis provided for First Line Treatment Choice by Asia Pacific Country by Tumour EGFR Mutation Status

Serious Adverse Events

Time Frame	N/A
Additional Description	Not applicable - no safety data collected in the study

Reporting Groups

	Description
China	Subjects in China that meet I/E and population criteria.
Taiwan	Subjects in Taiwan that meet I/E and population criteria
South Korea	Subjects in South Korea that meet I/E and population criteria
Australia	Subjects in Australia that meet I/E and population criteria
Thailand	Subjects in Thailand that meet I/E and population criteria
Singapore	Subjects in Singapore that meet I/E and population criteria
Malaysia	Subjects in Malaysia that meet I/E and population criteria
Indonesia	Subjects in Indonesia that meet I/E and population criteria
Russia	Subjects in Russia that meet I/E and population criteria

Serious Adverse Events

	China	Taiwan	South Korea	Australia	Thailand	Singapore	Malaysia	Indonesia	Russia
Total, serious adverse events
# participants affected / at risk	0/0	0/0	0/0	0/0	0/0	0/0	0/0	0/0	0/0

Other Adverse Events

Time Frame	N/A
Additional Description	Not applicable - no safety data collected in the study

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
China	Subjects in China that meet I/E and population criteria.
Taiwan	Subjects in Taiwan that meet I/E and population criteria
South Korea	Subjects in South Korea that meet I/E and population criteria
Australia	Subjects in Australia that meet I/E and population criteria
Thailand	Subjects in Thailand that meet I/E and population criteria
Singapore	Subjects in Singapore that meet I/E and population criteria
Malaysia	Subjects in Malaysia that meet I/E and population criteria
Indonesia	Subjects in Indonesia that meet I/E and population criteria
Russia	Subjects in Russia that meet I/E and population criteria

Other Adverse Events

	China	Taiwan	South Korea	Australia	Thailand	Singapore	Malaysia	Indonesia	Russia
Total, other (not including serious) adverse events
# participants affected / at risk	0/0	0/0	0/0	0/0	0/0	0/0	0/0	0/0	0/0

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description:

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Haiyi Jiang/Asia Medical Director
Organization:	AstraZeneca
Phone	+86 21 60302408
E-mail:	[email protected]

Documents available

D7913C00074_CSR_Synopsis
Download
Redacted Protocol
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Contact Backup

Esther Pascual

+34 91 301 9224

esther.pascual@astrazeneca.com

Investigators

Principal Investigator

Rose McCormack

AstraZeneca, PHB

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site