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KEYNOTE-059 cohort 2: Safety and efficacy of pembrolizumab (pembro) plus 5-fluorouracil (5-FU) and cisplatin for first-line (1L) treatment of advanced gastric cancer

Yung-Jue Bang, Kei Muro, Charles S. Fuchs, Talia Golan, Ravit Geva, Hiroki Hara, et al.

J Clin Oncol 35, 2017 (suppl; abstr 4012)

Editorial comment from Prof Lordick & Dr Smyth:
The results from Keynote 059 cohort 2 show that the anti PD-1 antibody pembrolizumab can be safely combined with standard cisplatin and fluoropyrimidine chemotherapy for treating patients with gastric cancer.    In this relatively small study, radiological response rates were encouraging (ORR 60%) as was overall survival (13.8 months).  Depending on the results of ongoing trials chemotherapy plus checkpoint inhibitors may also be an option for patients with advanced gastroesophageal cancer.



Preliminary analyses from the global, multicohort, phase 2 KEYNOTE-059 (NCT02335411) study suggested that safety of pembro + 5-FU + cisplatin is manageable as 1L therapy in pts with advanced gastric or gastroesophageal junction (G/GEJ) cancer (cohort 2). We present efficacy and updated safety data from KEYNOTE-059 cohort 2.


Cohort 2 enrolled pts ≥18 y with HER2– recurrent or metastatic G/GEJ adenocarcinoma, measurable disease, no prior therapy for metastatic/advanced disease, and ECOG PS 0-1. Pts received pembro 200 mg on day 1 of each 21-day cycle + cisplatin 80 mg/m2 for 6 cycles + 5-FU 800 mg/m2 (or capecitabine 1000 mg/m2 in Japan) Q3W for up to 2 y or until disease progression, investigator/pt decision to withdrawal, or unacceptable toxicity. PD-L1+pts had expression in ≥1% tumor or stromal cells using IHC (22C3 antibody). End points were safety and tolerability (primary), ORR (RECIST v1.1, by central review), DOR, PFS, and OS (secondary).


Of 25 enrolled pts, 64% were men, 68% were Asian, and 64% had PD-L1+ tumors. Median age was 64 y. At data cutoff (Oct 19, 2016), median duration of follow-up was 12.2 mo (range, 1.8 to 19.6) and 84% of pts had discontinued treatment, mainly owing to clinical or radiologic disease progression (64%). ORR (CR + PR) was 60% (95% CI, 38.7-78.9) in all pts. Overall, 32% of pts had SD (95% CI, 14.9-53.5), 4% had PD (95% CI, 0.1-20.4), and 4% were not evaluable (95% CI, 0.1-20.4). ORR was 68.8% (95% CI, 41.3-89.0) in PD-L1+ pts and 37.5% (95% CI, 8.5-75.5) in PD-L1– pts. Median DOR (range) was 4.6 mo (2.6 to 14.4+) in all pts, 4.6 mo (3.2 to 14.4+) in PD-L1+ pts, and 5.4 mo (2.8 to 8.3+) in PD-L1–pts. Median PFS was 6.6 mo (95% CI, 5.9-10.6); median OS was 13.8 mo (95% CI, 7.3-not estimable). Grade 3-4 treatment-related adverse events (TRAEs) occurred in 76% of pts. TRAEs led to discontinuation in 3 pts (grade 3 stomatitis, grade 2 hypoacusis, and grade 1 creatinine increase). No TRAEs were fatal.


Pembro + 5-FU + cisplatin showed manageable safety and encouraging antitumor activity as 1L therapy for pts with advanced G/GEJ cancer. Further exploration of pembro + 5-FU + cisplatin in this setting is warranted. Clinical trial information: NCT02335411

All content © 2017 American Society of Clinical Oncology. All rights reserved.

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