FDA approves Keytruda-Lenvima combination for advanced renal cell carcinoma
Click Here to Manage Email Alerts
The FDA approved the combination of pembrolizumab and lenvatinib for first-line treatment of adults with advanced renal cell carcinoma.
Pembrolizumab (Keytruda, Merck) is an anti-PD-1 therapy. Lenvatinib (Lenvima, Eisai) is a multiple receptor tyrosine kinase inhibitor.
The FDA previously approved the combination for treatment of women with advanced endometrial carcinoma that is not microsatellite instability-high or mismatch repair deficient whose disease progressed after systemic therapy and are not candidates for curative surgery or radiation.
The agency based the new indication on results of the randomized phase 3 CLEAR/KEYNOTE-581 trial, which included 1,069 patients (median age, 62 years; range, 29-88; 75% men; 74% white) with advanced renal cell carcinoma.
Researchers randomly assigned patients to one of three first-line regimens: 20 mg lenvatinib orally once daily in combination with 200 mg pembrolizumab administered via IV every 3 weeks for up to 24 months; 18 mg lenvatinib orally once daily in combination with 5 mg everolimus (Afinitor, Novartis) orally once daily; or 50 mg sunitinib (Sutent, Pfizer) orally once daily in a 4-weeks-on, 2-weeks-off schedule.
Treatment continued until disease progression or unacceptable toxicity.
PFS assessed by independent radiologic review and OS served as the major efficacy outcomes. Confirmed objective response rate assessed by independent review committee served as an additional efficacy outcome.
Patients assigned the pembrolizumab-lenvatinib combination achieved significantly longer PFS (median, 23.9 months vs. 9.2 months; HR = 0.39; 95% CI, 0.32-0.49) and OS (HR = 0.66; 95% CI, 0.49-0.88) than those assigned sunitinib. Patients assigned the combination also appeared more likely than those assigned sunitinib to achieve confirmed objective response (71% vs. 36%), complete response (16% vs. 4%) or partial response (55% vs. 32%).
“[The approval] is a significant milestone for newly diagnosed patients with advanced renal cell carcinoma and introduces a promising combination option in the first-line setting,” Robert J. Motzer, MD, Jack and Dorothy Byrne chair in clinical oncology and kidney cancer section head of the genitourinary oncology service at Memorial Sloan Kettering Cancer Center, said in an Eisai-issued press release.
The most common all-grade adverse reactions reported among patients assigned pembrolizumab-lenvatinib included fatigue (63%), diarrhea (62%), musculoskeletal disorders (58%), hypothyroidism (57%), hypertension (56%), stomatitis (43%), decreased appetite (41%), rash (37%) and nausea (36%).
The most common grade 3/grade 4 adverse reactions included hypertension (29%), diarrhea (10%), fatigue (9%), hepatotoxicity (9%), weight loss (8%) and proteinuria (8%).
About half (51%) of patients assigned the combination experienced serious adverse reactions, the most common of which were hemorrhagic events (5%), diarrhea (4%), hypertension (3%), myocardial infarction (3%), pneumonitis (3%), vomiting (3%), acute kidney injury (2%), adrenal insufficiency (2%), dyspnea (2%) and pneumonia (2%).
Fatal adverse reactions occurred among 4.3% of patients who received the combination. These included cardiorespiratory arrest (0.9%), sepsis (0.9%), and one case (0.3%) each of arrhythmia, autoimmune hepatitis, dyspnea, hypertensive crisis, increased blood creatinine, multiple organ dysfunction syndrome, myasthenic syndrome, myocarditis, nephritis, pneumonitis, ruptured aneurysm and subarachnoid hemorrhage.
Collapse
Read more about
Click Here to Manage Email Alerts