FDA Approves KEYTRUDA Combo for First-Line Treatment of Advanced Mesothelioma

Merck has announced that the U.S. Food and Drug Administration (FDA) has approved its anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in combination with pemetrexed and platinum chemotherapy. This approval is for the first-line treatment of adult patients with unresectable advanced or metastatic malignant pleural mesothelioma (MPM). This marks the first time KEYTRUDA has been approved for use in MPM in the United States.

The FDA's decision is based on results from the pivotal Phase 2/3 IND.227/KEYNOTE-483 trial, which demonstrated that the combination of KEYTRUDA and chemotherapy significantly improved overall survival (OS) compared to chemotherapy alone. Specifically, the study found that KEYTRUDA plus chemotherapy reduced the risk of death by 21% (HR=0.79 [95% CI, 0.64-0.98]; p=0.0162). The median OS for patients treated with the combination therapy was 17.3 months, compared to 16.1 months for those receiving chemotherapy alone.

In addition to overall survival, the trial also looked at progression-free survival (PFS) and overall response rate (ORR). Patients receiving KEYTRUDA plus chemotherapy had better PFS (HR=0.80 [95% CI, 0.65-0.99]; p=0.0194), with a median PFS of 7.1 months in both groups. The ORR was significantly higher in the combination therapy group at 52%, compared to 29% for chemotherapy alone.

However, the use of KEYTRUDA is not without risks. The therapy can cause immune-mediated adverse reactions, which may be severe or even fatal. These reactions can affect any organ system, potentially involving multiple systems simultaneously. They can occur at any point during or after treatment, making early identification and management crucial. Common adverse reactions include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, and complications related to organ transplants and stem cell transplantation. The drug can also cause infusion-related reactions and harm to a fetus if administered to a pregnant woman.

Dr. Gregory Lubiniecki, vice president of oncology clinical research at Merck Research Laboratories, expressed satisfaction with the approval, highlighting the company’s commitment to advancing treatments for difficult-to-treat tumors like MPM.

The IND.227/KEYNOTE-483 trial was a multicenter, randomized, open-label, active-controlled study conducted in collaboration with the National Cancer Institute of Naples and the Intergroupe Francophone de Cancérologie Thoracique. Merck provided KEYTRUDA and support for the trial, which included 440 patients with unresectable advanced or metastatic MPM who had not received prior systemic therapy for their advanced disease. Patients were randomized into two groups, with one receiving KEYTRUDA plus chemotherapy and the other receiving chemotherapy alone. Tumor status was assessed every six weeks for the first 18 weeks and then every 12 weeks thereafter. The primary measure of efficacy was overall survival, with additional measures including progression-free survival and overall response rate.

Malignant mesothelioma is a rare but aggressive form of cancer that affects the linings of the lungs, abdomen, heart, and testicles. Pleural mesothelioma, affecting the lung linings, is the most common form. The disease has a poor prognosis, with an estimated five-year survival rate of just 12.8% for cases diagnosed in the United States from 2014-2020.

KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby enhancing the immune system's ability to detect and fight tumor cells. Merck is conducting over 1,600 clinical trials to explore the efficacy of KEYTRUDA across various types of cancer and treatment settings.