As reported in The Lancet Oncology by Kohei Shitara, MD, and colleagues, interim analyses of the phase III KEYNOTE-585 trial have shown that the addition of perioperative pembrolizumab to chemotherapy improved pathologic complete response, but did not significantly improve event-free survival, in patients with locally advanced gastric/gastroesophageal cancer.
Kohei Shitara, MD
Study Details
The double-blind trial had a main cohort of 840 patients (48% Asian) from sites in 24 countries. They were randomly assigned between October 2017 and January 2021 to receive neoadjuvant pembrolizumab (n = 402) or placebo (n = 402) plus cisplatin-based chemotherapy every 3 weeks for 3 cycles, followed by surgery, adjuvant pembrolizumab or placebo plus chemotherapy for 3 cycles, then adjuvant pembrolizumab or placebo for 11 cycles. Primary endpoints were centrally reviewed pathologic complete response rate, investigator-assessed event-free survival, and overall survival in the intention-to-treat population.
Key Findings
Pathologic complete response was achieved in 12.9% of patients in the pembrolizumab group vs 2.0% of the control group (difference = 10.9%, 95% confidence interval [CI] = 7.5%–14.8%, P < .00001).
Median event-free survival was 44.4 months (95% CI = 33.0 months to not reached) vs 25.3 months (95% CI = 20.6–33.9 months) in the control group (hazard ratio [HR] = 0.81, 95% CI = 0.67–0.99, P = .0198), with the difference not achieving the predefined threshold for statistical significance (P = .0178). Median overall survival was 60.7 months (95% CI = 51.5 months to not reached) in the pembrolizumab group vs 58.0 months (95% CI = 41.5 months to not reached) in the control group (HR = 0.90, 95% CI = 0.73–1.12, P = .174).
Grade ≥ 3 adverse events occurred in 78% vs 74% of patients, most commonly nausea (60% vs 62%), anemia (42% vs 40%), and decreased appetite (41% vs 43%). Treatment-related serious adverse events occurred in 26% vs 24% of patients. Treatment-related adverse events led to death in four patients (1%) in the pembrolizumab group (interstitial ischemia, pneumonia, decreased appetite, and acute kidney injury in one each) and two patients (< 1%) in the control group (neutropenic sepsis and neutropenic colitis in one each).
The investigators concluded, “Although neoadjuvant and adjuvant pembrolizumab vs placebo improved the pathological complete response, it did not translate to significant improvement in event-free survival in patients with untreated, locally advanced resectable gastric or gastroesophageal cancer.”
Dr. Shitara, of the Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan, 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.
