Relationship between PD-L1 expression and clinical outcomes in patients with advanced gastric cancer treated with the anti-PD-1 monoclonal antibody pembrolizumab (MK-3475) in KEYNOTE-012.

Gastrointestinal (Noncolorectal) Cancer
Session Type and Session Title: 
Oral Abstract Session, Gastrointestinal (Noncolorectal) Cancer
Abstract Number: 


J Clin Oncol 33, 2015 (suppl; abstr 4001)
Yung-Jue Bang, Hyun-Choel Chung, Veena Shankaran, Ravit Geva, Daniel Virgil Thomas Catenacci, Shilpa Gupta, Joseph Paul Eder, Raanan Berger, Edward J. Gonzalez, Archana Ray, Marisa Dolled-Filhart, Kenneth Emancipator, Kumudu Pathiraja, Jared K. Lunceford, Jonathan D. Cheng, Minori Koshiji, Kei Muro; Seoul National University College of Medicine, Seoul, South Korea; Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea; University of Washington School of Medicine, Division of Medical Oncology, Seattle, WA; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; University of Chicago, Chicago, IL; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Yale Cancer Center, New Haven, CT; Sheba Medical Center, Tel HaShomer, Israel; Merck & Co., Inc., Kenilworth, NJ; Aichi Cancer Center Hospital, Nagoya, Japan

Abstract Disclosures


Background: Tumors use the PD-1 pathway to evade immune surveillance. Pembrolizumab, an anti–PD-1 monoclonal antibody, has shown antitumor activity in advanced cancers. We assessed the safety and efficacy of pembrolizumab in patients with advanced gastric cancer in KEYNOTE-012 (Clinicaltrials.gov identifier, NCT01848834). Methods: Archival tumor samples from patients from Asia-Pacific (AP) and rest of the world (ROW) with recurrent or metastatic adenocarcinoma of the stomach or gastroesophageal junction were screened for PD-L1 expression using a prototype IHC assay with the 22C3 antibody. Only patients with distinctive stromal or ≥ 1% tumor nest cell PD-L1 staining were eligible. Patients received pembrolizumab 10 mg/kg every 2 weeks for up to 24 months or until complete response, progression, or unacceptable toxicity. Imaging was performed every 8 weeks. Primary efficacy end point is ORR assessed per RECIST v1.1 by independent central review. Secondary end points include duration of response, PFS, and OS. Results: Of the 162 patients screened, 65 (40%) were PD-L1+. Of these 65 patients, 39 enrolled (19 from AP, 20 from ROW; median age, 63 years [range, 33-78]). The number of prior therapies for advanced disease ranged from 0 to 5; 67% received ≥ 2 prior therapies. Median follow-up duration was 8.8 months (range, 6.2-12.6); 13 patients (33%) remain on therapy. Four patients experienced 5 total grade 3-5 drug-related adverse events: peripheral sensory neuropathy, fatigue, decreased appetite, hypoxia, and pneumonitis (n = 1 each). There was 1 drug-related death (hypoxia). ORR was 22% (95% CI, 10-39) by central review and 33% (95% CI, 19-50) by investigator review. Median time to response was 8 weeks (range, 7-16), with a median response duration of 24 weeks (range, 8+ to 33+). PD-L1 expression level was associated with ORR (1-sided P = 0.10). The 6-month PFS rate was 24%. The 6-month OS rate was 69%. Conclusions: Pembrolizumab demonstrated manageable toxicity and promising antitumor activity in advanced gastric cancer. These results support the ongoing development of pembrolizumab for gastric cancer. Clinical trial information: NCT01848834