In IPASS (NCT00322452), 1217 Asian pts were randomised to 1st-line G (n = 609) or C/P (n = 608). Investigator-assessed progression-free survival (PFS; primary endpoint) significantly favoured G and C/P in the EGFR mutation-positive and -negative subgroups, respectively (Table). Objective response rate (ORR) followed a similar trend; median duration of response (DoR) with G was 8.7 months in pts with EGFR mutation-positive tumours (Table). Post hoc analyses of PFS, ORR and DoR according to BICR were requested by the FDA.
CT scans from pts with EGFR mutation-positive NSCLC were retrospectively collected post-study and reviewed by a third party (double read with adjudication paradigm with predefined assessment criteria for RECIST progression) independently of AstraZeneca. Reviewers were blinded to investigational site scan results and treatment assignment.
Scans from 186 pts with EGFR mutation-positive tumours were available for BICR (154 [82.8%] female, 178 [95.7%] never smokers, 175 [94.1%] WHO PS 0/1; consistent with the 261 EGFR mutation-positive population). According to BICR, at data cut-off (14 April 2008), 55 (62.5%) and 69 (70.4%) progression events had occurred in the G and C/P arms, respectively. Consistent with investigator assessment, PFS according to BICR significantly favoured G in the EGFR mutation-positive subgroup (n = 186; HR 0.544; 95% CI 0.375–0.786, p = 0.0012; median PFS 10.9 vs 7.4 months). Overall, BICR ORR and median DoR data were also consistent with investigator assessment (Table).
|EGFR mutation-positive (n = 261)||EGFR mutation-negative (n = 176)|
|PFS, HR (95% CI)||0.48 (0.36-0.64) p < 0.001||2.85 (2.05-3.98) p < 0.001|
|Median PFS G vs C/P, months||9.5 vs 6.3||1.5 vs 5.5|
|ORR, OR (95% CI)||2.75 (1.65-4.60) p = 0.0001||0.04 (0.01-0.27) p = 0.0013|
|EGFR mutation-positive population|
|Overall IPASS||IPASS BICR|
|G (n = 132)||C/P (n = 129)||G (n = 88)||C/P (n = 98)|
|ORR, % (95% CI)||71.2 (N/A)||47.3 (N/A)||67.1 (56.2-76.7)||40.8 (31.0-51.2)|
|Responders, n (%)||94 (71.2)||61 (47.3)||59 (67.0)||40 (40.8)|
|Non-responders, n (%)||38 (28.8)||68 (52.7)||29 (33.0)||58 (59.2)|
|Median DoR, months (95% CI)a||8.7 (N/A)||N/A||9.6 (7.4-12.5)||5.5 (4.1-5.7)|
HR, hazard ratio; N/A, not available; OR, odds ratio.
aPts with EGFR mutation-positive tumours who responded to G.
A subset of pts from the IPASS EGFR mutation-positive subgroup showed significant improvement in PFS, ORR and DoR with 1st-line G vs C/P when analysed by BICR, consistent with investigator assessment.
Clinical trial identification
T. Mok: honoraria: AstraZeneca (AZ), Roche (Ro), Eli Lilly (EL), Merck Serono (MS), Eisai, BMS, AVEO, Pfizer (Pf), Taiho, Boehringer Ingelheim (BI), Novartis, GSK, Clovis, Amgen (Am), Janssen, BioMarin; speaker: AZ, Ro, EL, BI, MS, Pf, Am; research funding: AZ. N. Saijo: grant support from: AstraZeneca, Chugai, Takeda, Taiho; owns equity in Takeda. S. Thongprasert: consultant fees from: AstraZeneca, Pfizer, Sanofi-Aventis; lecture fees from: AstraZeneca, Eli Lilly, Sanofi-Aventis; grant support from: AstraZeneca, Sanofi-Aventis, Pfizer. J.C.-H. Yang: honoraria: AstraZeneca (AZ), Boehringer Ingelheim (BI), Eli Lilly (EL), Pfizer (Pf), Roche (Ro); consultant: Astellas, AZ, Bayer, BI, Celgene, Clovis, Daiichi-Sankyo, EL, Merck, MSD, Novartis, Pf, Ro/Genentech; research funding: BI. Y.-L. Wu: speaker fees from: AstraZeneca, Roche, Eli Lilly, Pfizer, Sanofi. H. Young, V. Haddad, H. Jiang: employee of AstraZeneca and holds shares in AstraZeneca. M. Fukuoka: advisor for honoraria from: Asterus, Eisai, Chugai, Kyowa Hakko Kirin, Dainippon-Sumitomo, AstraZeneca.