In a phase II trial reported in JAMA Oncology, Manji et al found that perioperative chemotherapy and pembrolizumab showed activity in locally advanced resectable gastric and gastroesophageal junction adenocarcinoma.
Study Details
Thirty-four evaluable patients were enrolled in the investigator-initiated U.S. multicenter trial between February 2017 and June 2021. Patients received three cycles of capecitabine at 625 mg/m2 twice daily for 21 days, and oxaliplatin at 130 mg/m2 and pembrolizumab at 200 mg (with optional epirubicin at 50 mg/m2) every 3 weeks before and after surgery, with an additional cycle of pembrolizumab before surgery; patients then received 14 additional doses of maintenance pembrolizumab. The primary outcome measure was pathologic complete response rate, with a target of 15%.
Key Findings
Median follow-up was 35.2 months (range = 17.4–73.0 months). Among the 34 evaluable patients, 28 (82.4%) underwent curative resection.
Among the 34 patients, pathologic complete response was achieved in 7 (20.6%, 95% confidence interval [CI] = 10.1%–100%); an additional 6 (17.6%) achieved pathologic near-complete response. Among 21 patients with a PD-L1 combined positive score (CPS) of ≥ 1, the pathologic complete response rate was 23.8%; among 12 with a CPS of ≥ 10, the pathologic complete response rate was 33.3%.
Among 28 patients who underwent curative resection, 4 (14.3%) experienced disease recurrence. Median disease-free survival and overall survival were not reached. At 2 years, disease-free survival was 67.8% (95% CI = 0.53%–0.87%) and overall survival was 80.6% (95% CI = 0.68%–0.96%).
Among 35 patients in the safety population, treatment-related grade ≥ 3 adverse events occurred in 57.1% and immune-related grade ≥ 3 adverse events occurred in 34.3%. Adverse events led to death in three patients, with two (consisting of gastric hemorrhage and gastric perforation) being considered possibly related to treatment.
The investigators concluded, “In this trial of unselected patients with resectable gastric and gastroesophageal junction adenocarcinoma, capecitabine, oxaliplatin, and pembrolizumab resulted in a pathologic complete response rate of 20.6% and was well tolerated. This trial met its primary endpoint and supports the development of checkpoint inhibition in combination with perioperative chemotherapy in locally advanced gastric and gastroesophageal junction adenocarcinoma.”
Gulam A. Manji, MD, PhD, of the Division of Hematology and Oncology at Columbia University Irving Medical Center and Herbert Irving Comprehensive Cancer Center, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was funded by Merck Pharmaceuticals, National Cancer Institute grants, and others. For full disclosures of the study authors, visit jamanetwork.com.
