Welcome back to the D.I.S.C.O., FDA’s Drug Information Soundcast in Clinical Oncology, Burst Edition, brought to you by FDA’s Division of Drug Information in partnership with FDA’s Oncology Center of Excellence. Today we’ll be providing another quick update on a recent FDA cancer drug approval.
On March 22, 2021, the FDA approved pembrolizumab (brand name Keytruda) in combination with platinum and fluoropyrimidine-based chemotherapy for patients with metastatic or locally advanced esophageal or gastroesophageal carcinoma, with tumor epicenter 1 to 5 centimeters above the gastroesophageal junction, who are not candidates for surgical resection or definitive chemoradiation.
Efficacy was evaluated in KEYNOTE-590, 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 and progression-free survival, 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 overall survival and progression-free survival for patients randomized to pembrolizumab with chemotherapy. Median overall survival was 12.4 months for the pembrolizumab arm versus 9.8 months for the chemotherapy arm. Median progression-free survival was 6.3 and 5.8 months, respectively.
The most common adverse reactions reported in more than 20% of patients who received the pembrolizumab combination in the KEYNOTE-590 trial were nausea, constipation, diarrhea, vomiting, stomatitis, fatigue/asthenia, decreased appetite, and weight loss.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. The application reviews are ongoing at the other regulatory agencies.
This review also used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application approximately 3 weeks ahead of the FDA goal date.
Full prescribing information for this approval can be found on the web at www.fda.gov/drugsatFDA.
Health care professionals should report serious adverse events to FDA’s MedWatch Reporting System at www.fda.gov/medwatch.