Endometrial Cancer Indications Expanded for Pembrolizumab
The FDA approved pembrolizumab, in combination with chemotherapy, for certain patients with endometrial cancer.
The U.S. Food and Drug Administration (FDA) has approved pembrolizumab (Keytruda) plus the chemotherapies carboplatin and paclitaxel, followed by pembrolizumab alone, for the treatment of adult patients with advanced or recurrent endometrial carcinoma.
Pembrolizumab is an immunotherapy called an immune checkpoint inhibitor. It blocks the protein PD-1 on the surface of certain immune cells. PD-1 signaling dampens the immune response, preventing immune cells from killing cancer cells. Pembrolizumab inhibits this process, which boosts the immune system’s attack against the tumor. Cancer cells with defects in mismatch repair (dMMR), which may lead to high microsatellite instability (MSI-H) and high tumor mutation burden (TMB), may be more responsive to immune checkpoint inhibition.
This approval marks the 40th approved indication for pembrolizumab. For endometrial cancer, previously approved indications include: as a single-agent therapy for advanced or metastatic MSI-H, TMB, or dMMR tumors that have exhausted all other treatment options; in combination with lenvatinib (Lenvima) for patients whose tumors are not MSI-H/dMMR, have progressed after any other line of systemic therapy, and are not candidates for surgery or radiation; and as a single-agent therapy for patients whose tumors are MSI-H/dMMR, have progressed after any other line of systemic therapy, and are not candidates for surgery or radiation.
The current approval was based on results from the multicenter, randomized, double-blind, placebo-controlled, phase III KEYNOTE-868/NRG-GY018 clinical trial. The trial enrolled 810 patients with advanced or recurrent endometrial cancer who were randomly assigned to one of two treatment arms: pembrolizumab plus carboplatin and paclitaxel, followed by pembrolizumab alone, or placebo plus carboplatin and paclitaxel, followed by placebo alone.
Regardless of MMR status, patients in the pembrolizumab arm had significantly longer progression-free survival than those in the placebo arm. Among 222 patients with dMMR tumors, the median progression-free survival was not reached in the pembrolizumab arm, compared to 6.5 months in the placebo arm. Among 588 patients with mismatch repair-proficient tumors, the median progression-free survival was 11.1 months in the pembrolizumab arm and 8.5 months in the placebo arm.
The recommended dose of pembrolizumab is 200 mg every three weeks or 400 mg every six weeks until disease progression, unacceptable toxicity, or the patient has received treatment for 24 months.
Endometrial cancer is a type of cancer that affects the lining of the uterus. According to federal statistics, it was estimated that 67,880 individuals would be diagnosed with endometrial cancer and 13,250 patients would die of the disease in the United States in 2024.
The FDA rendered its decision on June 17, 2024.
