Pembrolizumab received FDA approval as initial treatment for esophageal and gastroesophageal junction cancer

For metastatic or locally advanced unresectable cancer, or when patients are not candidates for definitive radiotherapy, a treatment for esophageal or gastroesophageal junction cancer combining platinum- and fluoropyrimidine-based chemotherapy with the immunotherapy pembrolizumab (Keytruda) received approval on March 22, 2021 from FDA (the US Food and Drug Administration).

FDA approval based on the KEYNOTE-590 study

Efficacy was evaluated in KEYNOTE-590 (NCT03189719), a multicenter, randomized, placebo-controlled study involving 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 determined centrally in tumor samples from all patients using the PD-L1 IHC 22C3 PharmDx kit. Patients were randomized 1:1 to pembrolizumab combined with cisplatin and fluorouracil or placebo with cisplatin and fluorourasil until unacceptable toxicity or disease progression.

The main efficacy outcome measures were overall survival (OS) and progression-free survival (PFS), assessed by investigators according to RECIST 1.1 (modified to follow a maximum of 10 target lesions per organ and a maximum of 5 target lesions). The study showed statistically significant improvements in OS and PFS in patients randomized to pembrolizumab with chemotherapy. Median OS was 12.4 months (95% CI: 10.5, 14.0) in the pembrolizumab arm versus 9.8 months (95% CI: 8.8, 10.8) in 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).

The most common adverse reactions reported in ≥% 20 of patients receiving 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.