David H. Ilson, MD, PhD reviewing Muro K et al. Lancet Oncol 2016 May 3.
Duration of response justifies further study.
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.
Muro K et al. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): A multicentre, open-label, phase 1b trial. Lancet Oncol 2016 May 3; S1470-2045(16)00175-3; [e-pub].