FDA Approves Merck’s Keytruda in Combination with Chemotherapy for First-Line Treatment of Esophageal and Gastroesophageal Junction Carcinoma

Compiled by Fan Dongdong

Recently, the U.S. FDA approved Merck’s Keytruda (pembrolizumab) in combination with platinum- and fluoropyrimidine-based chemotherapy for the treatment of metastatic or locally advanced esophageal and gastroesophageal junction (GEJ) cancers that are not amenable to surgical resection or chemoradiation.

KEYNOTE-590 (NCT03189719) was a multicenter, randomized, placebo-controlled trial that enrolled a total of 749 patients with metastatic or locally advanced esophageal or gastroesophageal junction cancer who were not candidates for surgical resection or chemoradiotherapy, to evaluate the efficacy of pembrolizumab. The PD-L1 status of tumor specimens from all patients was assessed using the PD-L1 IHC 22C3 pharmDx kit. Patients were randomly assigned in a 1:1 ratio to receive either pembrolizumab plus cisplatin and fluorouracil or placebo plus cisplatin and fluorouracil, until drug toxicity or disease progression precluded further treatment.

The trial results demonstrated statistically significant improvements in overall survival (OS) and progression-free survival (PFS) in both groups of subjects. The median OS for patients receiving pembrolizumab was 12.4 months (95% CI: 10.5, 14.0), compared with 9.8 months (95% CI: 8.8, 10.8) in the chemotherapy group. The median PFS was 6.3 months (95% CI: 6.2, 6.9) for patients receiving pembrolizumab, versus 5.8 months (95% CI: 5.0, 6.0) for the chemotherapy group.

In KEYNOTE-590, the most commonly reported adverse reactions (≥20%) in patients receiving pembrolizumab combination therapy were nausea, constipation, diarrhea, vomiting, stomatitis, fatigue/asthenia, decreased appetite, and weight loss. The recommended dosage of pembrolizumab for esophageal cancer is 200 mg every 3 weeks or 400 mg every 6 weeks.

Merck & Co., Inc. reported full-year revenue of $48 billion last year, a 2% year-over-year increase, with pharmaceutical sales reaching $43 billion and animal health revenue amounting to $4.703 billion. As Merck’s flagship product, Keytruda generated $14.4 billion in sales in 2020, representing a 30% year-over-year growth and contributing 33% of the company’s pharmaceutical business performance. According to Merck, Keytruda’s clinical development program includes more than 400 clinical studies covering over 30 tumor types, with at least half of these studies investigating combination therapies involving Keytruda and other drugs.

Just last week, MSD announced that the European Commission had approved a label expansion for its anti-PD-1 therapy Keytruda. As a monotherapy, it is indicated for the treatment of adult and pediatric patients aged 3 years and older with relapsed or refractory classical Hodgkin lymphoma (cHL) who have failed autologous stem cell transplantation (ASCT) or have received at least two prior therapies when ASCT is not suitable. This marks the first pediatric approval for Keytruda in the EU. This week, MSD and Eisai jointly announced that their combination therapy, comprising the PD-1 inhibitor Keytruda and the tyrosine kinase inhibitor Lenvima, met both primary endpoints in a Phase 3 clinical trial involving previously treated patients with advanced, metastatic, or recurrent endometrial cancer. Compared to chemotherapy, the regimen significantly improved patients’ progression-free survival (PFS) and overall survival (OS).

Reference Source: FDA approves pembrolizumab for esophageal or GEJ carcinoma