General Information

Keytruda (pembrolizumab) is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. 

Keytruda is specifically indicated in combination with axitinib for the first-line treatment of patients with advanced renal cell carcinoma.

Keytruda is supplied as an injection for intravenous administration. The recommended dose of Keytruda for renal cell carcinoma is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks in combination with 5 mg axitinib orally twice daily until disease progression, unacceptable toxicity, or for Keytruda, up to 24 months in patients without disease progression. When axitinib is used in combination with Keytruda, dose escalation of axitinib above the initial 5 mg dose may be considered at intervals of six weeks or longer. 

Clinical Results

FDA Approval

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

The FDA approval of Keytruda for RCC was based on the pivotal Phase 3 KEYNOTE-426 trial. The randomized, multi-center, open-label trial was conducted in 861 patients who had not received systemic therapy for advanced RCC. Patients were enrolled regardless of PD-L1 tumor expression status. Randomization was stratified by International Metastatic RCC Database Consortium (IMDC) risk categories (favorable versus intermediate versus poor) and geographic region (North America versus Western Europe versus “Rest of the World”). Patients with active autoimmune disease requiring systemic immunosuppression within the last two years were ineligible. The patients were randomized (1:1) to one of the following treatment arms:

• Keytruda 200 mg intravenously every three weeks up to 24 months in combination with axitinib 5 mg orally, twice daily (n=432).
• Sunitinib 50 mg orally, once daily for four weeks and then off treatment for two weeks (n=429).

Treatment with the Keytruda-axitinib combination continued until RECIST v1.1 (modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ)-defined progression of disease or unacceptable toxicity. The main efficacy outcome measures were OS and PFS as assessed by BICR according to modified RECIST v1.1. Additional efficacy outcome measures included ORR, as assessed by BICR. For the main efficacy outcome measures of OS and PFS, the Keytruda-axitinib combination reduced the risk of death by 47% compared to sunitinib (p<0.0001); for PFS, the Keytruda-axitinib combination showed a reduction in the risk of progression of disease or death of 31% compared to sunitinib (p=0.0001). The ORR, an additional efficacy outcome measure, was 59% for patients who received the Keytruda-axitinib combination and 36% for those who received sunitinib (p<0.0001).

Side Effects

Adverse effects associated with the use of Keytruda in combination with axitinib may include, but are not limited to, the following:

diarrhea

fatigue/asthenia

hypertension

hepatotoxicity

hypothyroidism

decreased appetite

palmar-plantar erythrodysesthesia

nausea

stomatitis/mucosal inflammation

dysphonia

rash

cough

constipation

Mechanism of Action

Keytruda (pembrolizumab) is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Additional Information

For additional information regarding Keytruda or renal cell carcinoma, please visit https://www.keytruda.com/