The Food and Drug Administration (FDA) has approved pembrolizumab (Keytruda) plus lenvatinib (Lenvima) for the treatment of advanced renal cell carcinoma (RCC).
RCC is a kidney cancer that originates in the lining of the proximal convoluted tubule. Most cases of RCC are discovered incidentally during imaging tests for other abdominal diseases. Approximately 30% of patients with RCC will have advanced RCC at time of diagnosis. Survival is highly dependent on the stage of the cancer at diagnosis, and the five-year survival rate is 13% for patients diagnosed with advanced RCC.
The approval of pembrolizumab plus lenvatinib was largely based on data from the CLEAR trial (NCT02811861), a phase 3, open-label, randomized trial conducted in 1069 patients with advanced RCC. Patients were randomized (1:1:1) into one of three treatment arms:
- Lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously (IV) every 3 weeks for up to 24 months)
- Lenvatinib (20 mg orally once daily) plus everolimus (5 mg orally once daily)
- Sunitinib (50 mg orally once daily for 4 weeks on treatment, followed by 2 weeks off treatment).
The primary outcome measure was progression-free survival (PFS), as assessed by independent radiologic review (IRC). Additional efficacy outcome measures included confirmed overall response rate (ORR), also assessed by IRC. The results demonstrate that pembrolizumab plus lenvatinib demonstrated statistically significant improvements in PFS, overall survival, and ORR compared with sunitinib.
Median PFS was 23.9 months in the lenvatinib plus pembrolizumab treated group compared to only 9.2 months in the sunitinib treated group. ORR was 71% in the lenvatinib plus pembrolizumab treated group compared to 36% in the sunitinib treated group.
The most common adverse reactions (All Grades ≥20%) for pembrolizumab plus lenvatinib were fatigue (63%), diarrhea (62%), musculoskeletal disorders (58%), hypothyroidism (57%), hypertension (56%), stomatitis (43%), decreased appetite (41%), rash (37%), nausea (36%), weight loss, dysphonia and proteinuria (30% each), PPE syndrome (29%), hemorrhagic events (27%), abdominal pain (27%), vomiting (26%), constipation and hepatotoxicity (25% each), headache (23%), and acute kidney injury (21%). Clinically relevant adverse reactions (<20%) that occurred in patients receiving pembrolizumab plus lenvatinib were myocardial infarction (3%) and angina pectoris (1%).
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