FDA has approved MSD's KEYTRUDA (pembrolizumab) plus platinum- and fluoropyrimidine-based chemotherapy

MSD has announced that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA^®, MSD’s anti-PD-1 therapy, for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation in combination with platinum- and fluoropyrimidine-based chemotherapy.

The approval is based on results from the Phase 3 KEYNOTE-590 trial, which demonstrated significant improvements in overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) for KEYTRUDA plus fluorouracil (FU) and cisplatin versus FU and cisplatin alone, regardless of histology or PD-L1 expression status. For OS and PFS, KEYTRUDA plus FU and cisplatin reduced the risk of death by 27% (HR=0.73 [95% CI, 0.62-0.86]; p<0.0001) and reduced the risk of disease progression or death by 35% (HR=0.65 [95% CI, 0.55-0.76]; p<0.0001) versus FU and cisplatin alone. The ORR, an additional efficacy outcome measure, was 45% (95% CI, 40-50) for patients who received KEYTRUDA plus FU and cisplatin and 29% (95% CI, 25-34) for those who received FU and cisplatin alone (p<0.0001).

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of KEYTRUDA. Based on the severity of the adverse reaction, KEYTRUDA should be withheld or permanently discontinued, and corticosteroids administered if appropriate. KEYTRUDA can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman.

“Because esophageal cancer generally has poor survival rates, new first-line therapies are urgently needed for these patients,” said Dr. Peter Enzinger, Director, Center for Esophageal and Gastric Cancer, Dana-Farber/Brigham and Women’s Cancer Center. “Today’s approval of this indication for KEYTRUDA introduces a new option, which has shown a superior survival benefit compared to FU and cisplatin alone, for newly diagnosed patients with locally advanced or metastatic esophageal or GEJ carcinoma that is not amenable to surgical resection or definitive chemoradiation, regardless of PD-L1 expression status and tumor histology.”

“There have been few advances in improving survival outcomes in the first-line treatment setting for esophageal cancer over the last three decades,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, MSD Research Laboratories. “We are committed to putting patients first and continuing our research to help advance new approaches to potentially extend the lives of people with cancer. We thank all of the patients, their caregivers and healthcare professionals who participated in the study.”

This approval was reviewed under the FDA’s Real-Time Oncology Review (RTOR) pilot program and the FDA’s Project Orbis, an initiative of the Oncology Center of Excellence that provides a framework for concurrent review of oncology drugs among its international partners. Under this project, the FDA, Australian Therapeutic Goods Administration, Health Canada and Swissmedic collaboratively reviewed the KEYNOTE-590 application. The application is still under review in Australia, Canada and Switzerland.

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