As reported in the Journal of Clinical Oncology by Shitara et al, the final overall survival analysis from the phase III KEYNOTE-585 study showed a numeric—but statistically nonsignificant—benefit with pembrolizumab plus chemotherapy vs chemotherapy in perioperative therapy for patients with resectable, locally advanced gastric and gastroesophageal junction cancers.
Study Details
In the international double-blind trial, 804 patients in the main trial cohort were randomly assigned between October 2017 and January 2021 to receive perioperative pembrolizumab (n = 402) or placebo (n = 402) plus neoadjuvant chemotherapy with cisplatin plus capecitabine or fluorouracil every 3 weeks followed by adjuvant pembrolizumab or placebo plus chemotherapy for 3 cycles, followed by pembrolizumab or placebo for 11 cycles. In the primary analysis, the pembrolizumab group had a significantly better pathologic complete response rate and a numeric, but not statistically significant, benefit in event-free survival.
Key Findings
At final analysis (data cutoff in February 2024), median follow-up was 59.9 months (range = 39.0–75.8 months). Median overall survival was 71.8 months (95% confidence interval [CI] = 52.5 months to not reached) in the pembrolizumab group vs 55.7 months (95% CI = 41.7 months to not reached) in the control group (hazard ratio [HR] = 0.86, 95% CI = 0.71–1.06); the 5-year overall survival rate was 54% vs 48%. Updated pathologic complete response data showed a rate of 13.4% vs 2.0% (difference = 11.4%, 95% CI = 8.0%–15.3%). Median event-free survival at the time of final analysis was 44.4 months (95% CI = 33.0– 69.8 months) in the pembrolizumab group vs 25.7 months (95% CI = 20.8–36.5 months) in the control group (HR = 0.81, 95% CI = 0.67–0.98); the 5-year event-free survival rate was 47% vs 37%.
No new safety concerns were observed. Overall, grade ≥ 3 drug-related adverse events were reported in 65% of the pembrolizumab group vs 63% of the control group. No worsening of health-related quality of life was observed in the pembrolizumab group vs the control group.
The investigators stated: “Pembrolizumab plus chemotherapy continued to show improved outcomes in [pathologic complete response] and a trend toward longer [event-free survival] versus placebo…. Efficacy and safety outcomes with perioperative pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab in participants with untreated, locally advanced resectable [gastric and gastroesophageal junction] cancer were consistent with previous analyses.”
Kohei Shitara, MD, of the National Cancer Center Hospital East, Kashiwa, Japan, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. For full disclosures of all study authors, visit ascopubs.org.
