Annals of Oncology
Volume 30 | Supplement 3 | May 2019
Volume 30 | Supplement 5 | October 2019
K. Shitara1 , E. Van Cutsem2 , Y-J. Bang3 , C.S. Fuchs4 , L. Wyrwicz5 , K.W. Lee6 , I. Kudaba7 , M. Garrido8 , H. Cheol Chung9 , H.R. Castro10, W. Mansoor11, M.I.F.M. Braghiroli12, E. Goekkurt13, J. Chao14, Z.A. Wainberg15, U. Kher16, S. Shah16, S.P. Kang16, J. Tabernero17
1 Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan, 2 Digestive Oncology, University Hospitals Leuven - Campus Gasthuisberg, Leuven, Belgium, 3 Medical Oncology, Seoul National University Hospital, Seoul, Republic of Korea, 4 Medical Oncology, Yale Cancer Center, New Haven, CT, USA, 5 Medical Oncology, Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie, Klinika Gastroenterologii Onkologicznej, Warsaw, Poland, 6 Medical Oncology, Seoul National University Bundang Hospital, Seoul, Republic of Korea, 7 Oncology, Latvian Oncology Center Rakus Gailezers, Riga, Latvia, 8 Medical Oncology, Pontificia Universidad Catolica de Chile, Santiago, Chile, 9 Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea, 10Oncology, Grupo Medico Angeles, Guatemala, Guatemala, 11Oncology, The Christie NHS Foundation Trust, Manchester, UK, 12Medical Oncology, ICESP - Instituto do Cancer do Estado de Sao Paulo, S~ao Paulo, Brazil, 13HOPE, Hematology Oncology Practice Eppendorf (Facharztzentrum Eppendorf), Hamburg, Germany, 14Department of Medical Oncology and Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA, 15Oncology, Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA, 16Oncology, Merck & Co., Inc., Kenilworth, NJ, USA, 17Medical Oncology, Vall d’Hebron University Hospital. Vall d’Hebron Institute of Oncology VHIO., Barcelona, Spain
Background: KEYNOTE-062 (NCT02494583) was a randomized, study of 1L pembrolizumab (P) or pembro þ chemo (PþC) vs chemo (C) in patients (pts) with PD-L1 combined positive score 1 (CPS 1), HER2-negative, advanced GC.
Methods: Eligible pts were randomized 1:1:1 to P 200 mg Q3W for up to 2 y, PþC (cisplatin 80 mg/m2 þ 5-FU 800 mg/m2 /d on d1-d5 Q3W [or capecitabine 1000 mg/m2 BID on d1-d14 Q3W per local guideline]) or placebo Q3W þ C. Primary endpoints were OS in CPS 1 and CPS 10 for PþC vs C and P vs C and PFS (RECIST v1.1; central review) in CPS 1 for PþC vs C. ORR (RECIST v1.1; central review) in CPS 1 for PþC vs C was the secondary endpoint. The final analysis cutoff date was 26 Mar 2019. Results: 763 pts (281 with CPS 10) were randomized to PþC (257), P (256), or C (250) (Table). Median follow-up was 11.3 mo. P was noninferior to C for OS in CPS 1 per prespecified margins. P vs C prolonged OS in CPS 10 (median 17.4 vs 10.8 mo; HR 0.69; 95% CI 0.49-0.97) but wasn’t tested per analysis plan. PþC vs C was not superior for OS in CPS 1 or CPS 10, with a favorable trend for PþC. In an exploratory analysis of pts with MSI-H tumors with CPS 1 (N ¼ 50), median OS was not reached vs 8.5 mo for both P vs C (HR 0.29; 95% CI 0.11-0.81) and PþC vs C (HR 0.37; 95% CI 0.14-0.97). PFS was longer with P vs C (HR 0.72; 95% CI 0.31-1.68) and PþC vs C (HR 0.45; 95% CI 0.18-1.11). ORR was higher with P (57%) and P þ C (65%) vs C (37%). Median DOR was 21.2 mo with P, not reached (P þ C) vs 7.0 mo (C). Grade 3-5 drugrelated AE rates were 17% (P), 73% (PþC), and 69% (C). Conclusions: As 1L therapy for advanced GC, P was noninferior to C for OS in CPS 1 with clinically meaningful improvement for OS in CPS 10. PþC did not show superior OS and PFS in CPS 1 and OS in CPS 10. Clinical benefit was substantially enhanced in a small subset of pts with MSI-H tumors. The safety profile was more favorable for P vs C.
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