The FDA has approved the combination therapy of pembrolizumab plus lenvatinib for patients with spec

On July 22, 2021, Merck & Co., Inc. and Eisai Co., Ltd. jointly announced that the U.S. Food and Drug Administration (FDA) had approved Merck’s anti-PD-1 therapy pembrolizumab in combination with Eisai’s discovered oral multi-receptor tyrosine kinase inhibitor lenvatinib for the treatment of adult patients with advanced endometrial carcinoma who are non-microsatellite instability-high (non-MSI-H) or proficient mismatch repair (pMMR). These patients have experienced disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation therapy.

This approval for this patient population was based on the results of the pivotal Phase 3 clinical trial KEYNOTE-775/Study 309. In this trial, compared with chemotherapy (investigator’s choice of doxorubicin or paclitaxel), the combination of pembrolizumab and lenvatinib demonstrated a statistically significant improvement in overall survival (OS), reducing the risk of death by 32% (hazard ratio [HR] = 0.68 [95% confidence interval, 0.56–0.84]; p = 0.0001). It also showed a statistically significant improvement in progression-free survival (PFS), decreasing the risk of disease progression or death by 40% (HR = 0.60 [95% CI, 0.50–0.72]; p < 0.0001).

In addition, the combination of pembrolizumab and lenvatinib yielded a statistically significant improvement in objective response rate (ORR), reaching 30% (95% CI, 26–36), in contrast to the 15% ORR (95% CI, 12–19) observed in patients who received the investigator’s choice of doxorubicin or paclitaxel. Among these, the complete response (CR) rate was 5% in the pembrolizumab-lenvatinib combination group versus 3% in the doxorubicin or paclitaxel group, and the partial response (PR) rate was 25% versus 13%, respectively.

Immune-mediated adverse reactions can occur in any organ system or tissue, may affect multiple body systems simultaneously, and can be severe or even fatal. Such reactions can occur at any time during or after pembrolizumab treatment, including pneumonitis, colitis, hepatitis, endocrine disorders, nephritis, dermatologic adverse reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation. The important immune-mediated adverse reactions listed herein may not cover all possible severe and fatal immune-mediated adverse reactions. Early identification and management of immune-mediated adverse reactions are critical to ensure the safe use of pembrolizumab. Depending on the severity of the adverse reaction, pembrolizumab should be withheld or permanently discontinued, and corticosteroid therapy should be administered as appropriate.