From the Research
The KEYNOTE-585 trial is a significant study that demonstrates the efficacy of pembrolizumab in combination with chemotherapy for patients with locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, with improved pathological complete response and event-free survival compared to chemotherapy alone 1.
Key Findings
- The trial evaluated the combination of pembrolizumab 200 mg intravenously every 3 weeks with cisplatin-based doublet chemotherapy, followed by surgery, adjuvant pembrolizumab or placebo plus chemotherapy, and then adjuvant pembrolizumab or placebo for 11 cycles.
- The primary endpoints were pathological complete response, event-free survival, and overall survival in the intention-to-treat population, with safety assessed in all patients who received at least one dose of study treatment.
- The results showed that pembrolizumab was superior to placebo for pathological complete response, with a difference of 10.9% (95% CI 7.5 to 14.8; p<0.00001) 1.
Treatment Regimen
- The recommended regimen includes pembrolizumab 200 mg intravenously every 3 weeks along with cisplatin 80 mg/m² on day 1 and either 5-fluorouracil 800 mg/m² daily for 5 days or capecitabine 1000 mg/m² twice daily for 14 days, in 21-day cycles.
- Treatment continues for up to 35 cycles of pembrolizumab (approximately 2 years) or until disease progression or unacceptable toxicity.
Adverse Events
- The most common adverse events include nausea, fatigue, decreased appetite, and immune-related effects such as hypothyroidism and colitis.
- Grade 3 or worse adverse events of any cause occurred in 78% of patients in the pembrolizumab group and 74% of patients in the placebo group 1.
Mechanism of Action
- The immunotherapy works by blocking the PD-1 pathway, enhancing T-cell activity against tumor cells, while the chemotherapy directly damages cancer cell DNA, providing a dual mechanism of action against gastric cancer.
Monitoring
- Patients should be monitored regularly with imaging every 6-9 weeks, thyroid function tests, and liver function tests.