On March 22, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda) in combination with platinum and fluoropyrimidine-based chemotherapy for patients with metastatic or locally advanced esophageal or gastroesophageal junction (tumors with epicenter 1–5 cm above the gastroesophageal junction) carcinoma who are not candidates for surgical resection or definitive chemoradiation.
Efficacy was evaluated in KEYNOTE-590 (ClinicalTrials.gov identifier NCT03189719), a multicenter, randomized, placebo-controlled trial that enrolled 749 patients with metastatic or locally advanced esophageal or gastroesophageal junction carcinoma who were not candidates for surgical resection or definitive chemoradiation. PD-L1 status was centrally determined in tumor specimens in all patients using the PD-L1 IHC 22C3 pharmDx kit. Patients were randomly assigned 1:1 to receive either pembrolizumab in combination with cisplatin and fluorouracil or placebo with cisplatin and fluorouracil, until unacceptable toxicity or disease progression.
The main efficacy outcome measures were overall survival and progression-free survival, as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ).
The trial demonstrated a statistically significant improvement in overall and progression-free survival for patients treated with pembrolizumab plus chemotherapy. Median overall survival was 12.4 months (95% confidence interval [CI] = 10.5–14.0) for the pembrolizumab arm vs 9.8 months (95% CI = 8.8–10.8) for the chemotherapy arm (hazard ratio [HR] = 0.73, 95% CI = 0.62–0.86, P < .0001). Median progression-free survival was 6.3 (95% CI = 6.2–6.9) and 5.8 months (95% CI = 5.0–6.0), respectively (HR = 0.65, 95% CI = 0.55–0.76, P < .0001).
The most common adverse reactions reported in ≥ 20% of patients who received the pembrolizumab combination in KEYNOTE-590 were nausea, constipation, diarrhea, vomiting, stomatitis, fatigue/asthenia, decreased appetite, and weight loss.
The recommended pembrolizumab dose for esophageal cancer is 200 mg every 3 weeks or 400 mg every 6 weeks.