Pembrolizumab Has Promising Activity in PD-L1–Positive Gastric Cancer

Summary and Comment |
May 19, 2016

Pembrolizumab Has Promising Activity in PD-L1–Positive Gastric Cancer

  1. David H. Ilson, MD, PhD

Duration of response justifies further study.

  1. David H. Ilson, MD, PhD

Chemotherapy for patients with metastatic gastric cancer achieves a median survival of less than 1 year. Newer agents such as trastuzumab in the first-line treatment of HER2-positive disease and ramucirumab in combination with second-line chemotherapy modestly improve response and survival. Treatment of chemotherapy refractory disease, however, represents an unmet need.

Investigators now report the results of an industry-sponsored, international, multicenter, single-arm, phase Ib trial of the anti–PD-1 antibody pembrolizumab (10 mg/kg every 2 weeks) in metastatic gastric cancer patients with immunohistochemistry-positive staining for PD-L1 in either tumor or stroma. PD-L1 positivity was seen in 40% of 162 patients screened. Of 39 enrolled patients, half were from Asia and half were from the rest of the world; most (67%) had received two or more prior chemotherapy regimens; and in 24 assessable patients, 4 (17%) had microsatellite instability (MSI). The gastroesophageal junction was the primary tumor location in 28%. Response rate was the primary endpoint.

Partial response by central review was seen in 8 of 36 evaluable patients (22%), with a median response duration of 40 weeks. Half of the responses appeared more durable. Progression-free survival was 1.9 months and overall survival 11.4 months. Higher interferon Υ gene expression signature and higher mononuclear inflammatory cell density score correlated with higher antitumor response. Two of the MSI-high patients responded. No new safety signals were observed.


Pembrolizumab has promising activity in patients with gastric cancer positive for PD-L1 expression. The median duration of response and the apparent durability of half of the responses are encouraging and justify the multiple ongoing phase II and III trials of anti–PD-1 and anti–PD-L1 therapies in esophagogastric cancer. A clear biomarker to predict response remains to be identified.

Editor Disclosures at Time of Publication

  • Disclosures for David H. Ilson, MD, PhD at time of publication Consultant / Advisory board Amgen; Eli Lilly–ImClone; Macrogenics; Bayer Speaker’s bureau Genentech/Roche Grant / Research support Bayer; Amgen; Bristol-Myers Squibb


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