DocWire NewsKEYNOTE-585: Neoadjuvant, Adjuvant Pembrolizumab for Locally Advanced Gastric or Gastroesophageal Cancer

Evaluating the Efficacy of Pembrolizumab in Combination with Chemotherapy for Advanced Gastric Cancers: Insights from a Phase 3 Study

In a pivotal phase 3 study, researchers led by Dr. Kohei Shitara explored the effectiveness of combining neoadjuvant and adjuvant pembrolizumab with chemotherapy for treating locally advanced, resectable gastric or gastroesophageal adenocarcinoma. This double-blind trial, published in The Lancet Oncology, provides critical insights into the antitumor activity of pembrolizumab in conjunction with established chemotherapy regimens, marking a significant step in understanding the treatment landscape for these challenging cancers.

Key Points:

1. Study Design: The study randomly assigned patients to receive neoadjuvant pembrolizumab (200 mg) or placebo plus cisplatin-based chemotherapy, followed by surgery and adjuvant pembrolizumab or placebo plus chemotherapy for 3 cycles, and then 11 cycles of adjuvant pembrolizumab or placebo.
2. Subsection Protocol: A subgroup of patients received pembrolizumab or placebo with fluorouracil, docetaxel, and oxaliplatin (FLOT)-based chemotherapy, followed by similar adjuvant treatment schedules.
3. Patient Demographics: The trial included 804 patients, with 402 in the pembrolizumab plus cisplatin-based chemotherapy group and 402 in the placebo group; within the FLOT subgroup, 100 received pembrolizumab and 103 received placebo.
4. Primary Endpoints: The study focused on pathological complete response, event-free survival, overall survival, and safety.
5. Pathological Complete Response: Pembrolizumab demonstrated an increased pathological complete response (95% CI, 9.8-16.6) compared to placebo.
6. Event-Free Survival: There was no significant improvement in event-free survival for the pembrolizumab group compared to placebo (44.4 months; 95% CI, 33.0 vs 25.3 months; 95% CI, 0.67-0.99; P=0·0198).
7. Researcher Conclusion: Although pembrolizumab improved pathological complete response, it did not significantly enhance event-free survival in patients with untreated, locally advanced resectable gastric or gastroesophageal cancer.

“Although neoadjuvant and adjuvant pembrolizumab versus 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. Kohei Shitara and colleagues

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