In the Japanese single-center phase II EPOC1706 trial reported in The Lancet Oncology, Kawazoe et al found high objective response among patients with advanced gastric cancer who received the combination of lenvatinib and pembrolizumab as first- or second-line treatment.
The trial included 29 patients with metastatic or recurrent adenocarcinoma of the stomach or gastroesophageal junction enrolled between October 2018 and March 2019 at the National Cancer Center Hospital East (Chiba). Patients received lenvatinib at 20 mg/d plus pembrolizumab at 200 mg every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate according to Response Evaluation Criteria in Solid Tumors version 1.1.
Median follow-up was 12.6 months. Objective response was observed in 20 (69%) of 29 patients, with complete response observed in 1 patient. Stable disease was observed in an additional nine patients (31%). Response was observed in 10 (71%) of 14 patients receiving treatment in the first-line setting and in 10 (67%) of 15 patients receiving the combination in the second-line setting. Median progression-free survival was 7.1 months (95% confidence interval [CI] = 5.4–13.7). Median overall survival was not reached (95% CI = 11.8 months–not reached).
In prespecified exploratory analyses, objective response was observed in 16 (84%) of 19 patients with a PD-L1 combined positive score (CPS) of ≥ 1 and in 4 (40%) of 10 with CPS < 1. Among these patients, median progression-free survival was 9.1 months and 5.9 months, respectively. Among 21 patients with tumor mutational burden (TMB) data, response was observed in 9 (82%) of 11 patients with a high TMB score (above the median of 10) and in 6 (60%) of 10 with a low TMB score.
Grade 3 treatment-related adverse events occurred in 14 patients (48%), with the most commonly reported being hypertension in 11 (38%), proteinuria in 5 (17%), and decreased platelet count in 2 (7%). No grade 4 treatment-related adverse events were observed.
Serious adverse events were observed in four patients (14%), including grade 2 obstructive jaundice, grade 3 heart failure, grade 3 gastric hemorrhage, and gastric perforation in one patient each; none of the events was considered treatment-related. No treatment-related deaths were reported.
The investigators concluded, “Lenvatinib plus pembrolizumab showed promising antitumor activity with an acceptable safety profile in patients with advanced gastric cancer. On the basis of these results, a confirmatory trial will be planned in the future.”
Kohei Shitara, MD, of the Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Merck Sharp & Dohme. For full disclosures of the study authors, visit thelancet.com.
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