FDA Approves Pembrolizumab for Esophageal or GEJ Carcinoma

The U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda, Merck Sharp & Dohme Corp.) in combination with platinum and fluoropyrimidine-based chemotherapy for patients with metastatic or locally advanced esophageal or gastroesophageal (GEJ) (tumors with epicenter 1 to 5 centimeters above the gastroesophageal junction) carcinoma who are not candidates for surgical resection or definitive chemoradiation.

Efficacy was evaluated in KEYNOTE-590 (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 randomized (1:1) to 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 (OS) and progression-free survival (PFS), as assessed by the investigator according to RECIST 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 OS and PFS for patients randomized to pembrolizumab with chemotherapy. Median OS was 12.4 months (95% CI: 10.5, 14.0) for the pembrolizumab arm versus 9.8 months (95% CI: 8.8, 10.8) for the chemotherapy arm (HR 0.73; 95% CI: 0.62, 0.86; p<0.0001). Median PFS 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<0.0001).

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.