Pembrolizumab is a checkpoint inhibitor that belongs to a class of drugs called monoclonal antibodies. Pembrolizumab binds to a protein called programmed cell death-1 (PD-1) on the surface of immune cells called T cells, and prevents it from interacting with another protein called programmed cell death-ligand 1 (PD-L1) on the surface of cancer cells. This interaction normally inhibits the activation and function of T cells, allowing cancer cells to escape immune surveillance and attack. By blocking this interaction, pembrolizumab enhances the ability of T cells to recognize and kill cancer cells.
Pembrolizumab, used in the treatment of renal cell carcinoma, is a checkpoint inhibitor and belongs to the class of drugs known as monoclonal antibodies. Source. |
Pembrolizumab and Axitinib for Renal Cell Carcinoma
Pembrolizumab has been approved by the FDA for the treatment of renal cell carcinoma in different settings. In 2019, pembrolizumab was approved in combination with axitinib for the first-line treatment of patients with advanced renal cell carcinoma. This approval was based on the results of a phase III trial called KEYNOTE-426, which showed that pembrolizumab plus axitinib significantly improved overall survival, progression-free survival, and objective response rate compared to sunitinib, another drug for renal cell carcinoma, in 861 patients with previously untreated advanced renal cell carcinoma (1).
Pembrolizumab and Lenvatinib for Renal Cell Carcinoma
In 2021, pembrolizumab was approved in combination with lenvatinib for the first-line treatment of patients with advanced renal cell carcinoma. This approval was based on the results of a phase III trial called CLEAR/KEYNOTE-581, which showed that pembrolizumab plus lenvatinib significantly improved overall survival, progression-free survival, and objective response rate compared to sunitinib in 1069 patients with previously untreated advanced renal cell carcinoma (2).
Pembrolizumab as Adjuvant for Renal Cell Carcinoma
In 2021, pembrolizumab was also approved as adjuvant therapy for patients with renal cell carcinoma at intermediate-high or high risk of recurrence following nephrectomy (surgical removal of the kidney) or following nephrectomy and resection of metastatic lesions. This approval was based on the results of a phase III trial called KEYNOTE-564, which showed that pembrolizumab significantly improved disease-free survival compared to placebo in 994 patients with renal cell carcinoma who had undergone nephrectomy with or without metastasectomy (3).
Pembrolizumab: Side Effects
Pembrolizumab for renal cell carcinoma is administered as an intravenous infusion every three weeks or every six weeks, depending on the indication and the regimen. The most common side effects of pembrolizumab include fatigue, musculoskeletal pain, rash, diarrhea, pruritus, hypothyroidism, cough, nausea, and decreased appetite. Pembrolizumab can also cause serious immune-related adverse events, such as pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin reactions, which may require corticosteroids or other immunosuppressive agents to manage.
Pembrolizumab: Summary
Pembrolizumab is a promising immunotherapy for renal cell carcinoma that has shown significant benefits in different settings and across different subgroups of patients. Pembrolizumab can be used alone or in combination with other agents to improve the outcomes of patients with advanced or metastatic renal cell carcinoma, or to reduce the risk of recurrence in patients with operable renal cell carcinoma. Pembrolizumab is generally well tolerated, but requires careful monitoring and management of potential immune-related adverse events.
Disclaimer: This blog post is intended solely for informational purposes. It is not meant to serve as medical advice. For professional medical guidance, please consult your doctor.
Further Reading
- Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 2019;380:1116-27.
- Motzer RJ, Alekseev B, Rha SY, et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med 2021;384:1289-300.
- Choueiri TK, Tomczak P, Park SH, et al. Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for patients with renal cell carcinoma: randomized, double-blind, phase III KEYNOTE-564 study. J Clin Oncol 2021;39:2805-16.
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