Renal cell carcinoma.

Pembrolizumab (Keytruda®, Merck Inc.), previously FDA approved for various cancers, including advanced non-small cell lung cancer, classical Hodgkin lymphoma, and advanced gastric cancer, has now been granted FDA approval to be administered in conjunction with axitinib (Inlyta®, Pfizer Inc.) as first-line treatment for patients with locally advanced or metastatic renal cell carcinoma (RCC).

As an immunotherapy drug, pembrolizumab fights cancer by working with the patient's immune system. The drug effectively blocks the PD-1 pathway so that cancer cells are not able to evade attack from T cells, the body's natural immune defense. Axitinib, which works by preventing new blood vessels from forming, thereby hindering cancerous cell growth, had previously been approved for second-line treatment of metastatic RCC.

Approval of pembrolizumab/axitinib was based on a phase 3 trial (NCT02853331), published in the Journal of Clinical Oncology. In this study, 861 patients with locally advanced or metastatic RCC were randomized in a 1:1 ratio to receive either 200 mg pembrolizumab intravenously for three weeks plus 5 mg axitinib orally twice a day or 50 mg sunitinib orally; both groups received treatment on a 4-weeks-on, 2-weeks-off schedule. In order to be eligible for the study, patients must have received no previous systemic therapy for RCC and needed to have a Karnofsky Performance Status ³70%.

After a 12.8-month median follow-up, pembrolizumab/axitinib significantly improved overall survival (89.9% vs 78.3%), progression-free survival (15.1 vs 11.1 months), and objective response rate (59.3% vs 35.7%) compared with sunitinib monotherapy.

In one-fifth of participants, grade 3 or 4 hepatotoxicity occurred, causing permanent discontinuation of pembrolizumab or axitinib in 13% of patients. Common side effects include diarrhea, asthenia, hypertension, hypothyroidism, decreased appetite, hepatotoxicity, palmar-plantar erythrodysesthesia, nausea, stomatitis/mucosal inflammation, dysphonia, rash, cough, and constipation.

The study authors conclude, "Pembrolizumab plus axitinib provided superior OS, PFS, and ORR compared with sunitinib and had manageable safety in patients with previously untreated, advanced or metastatic clear-cell RCC. These data suggest that pembrolizumab plus axitinib should be a new standard of care for this population."

For More Information (2019). Study to evaluate the efficacy and safety of pembrolizumab (MK-3475) in combination with axitinib versus sunitinib monotherapy in participants with renal cell carcinoma (MK-3475-426/KEYNOTE-426). NLM identifier: NCT02853331.

Powles T, Plimack ER, Stus V, et al (2019). Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for locally advanced or metastatic renal cell carcinoma (mRCC): a phase III KEYNOTE-426 study. J Clin Oncol, 37. Abstract 543. 

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