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Lenvatinib improves survival for patients with RCC who progressed after initial treatment
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Patients with metastatic renal cell cancer who had progressed following VEGF-targeted therapy experienced a PFS benefit with lenvatinib alone or in combination with everolimus, according to findings from a phase 2 trial.
“Lenvatinib [Lenvima, Eisai] is a novel tyrosine kinase inhibitor that targets both the VEGF receptor as well as fibroblast growth factor receptors, which are felt to be important in drug resistance,” Robert J. Motzer, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, told HemOnc Today. “The study showed a higher response rate and improved PFS for lenvatinib over everolimus (Afinitor, Novartis). However the highest efficacy was seen with the combination of lenvatinib plus everolimus.”
Robert J. Motzer, MD
Motzer and colleagues sought to compare the efficacy and safety of the established maximum tolerated dose of lenvatinib alone or with everolimus among 153 patients with metastatic clear cell renal cell carcinoma who experienced disease progression after one previous VEGF-targeted therapy.
Researchers assigned 52 patients to receive lenvatinib alone (24 mg daily), 50 to everolimus alone (10 mg daily), and 51 to lenvatinib (18 mg daily) plus everolimus (5 mg daily).
Patients who received the combination achieved significantly prolonged PFS compared with patients assigned standard-care of everolimus alone (14.6 months vs. 5.5 months; HR = 0.4; 95% CI, 0.24-0.68) but not lenvatinib alone (7.4 months; HR = 0.66; 95% CI, 0.3-1.1).
Still, patients assigned lenvatinib achieved improved PFS compared with those assigned everolimus alone (HR = 0.61; 95% CI, 0.38-0.98).
Fewer grade 3 to grade 4 adverse events occurred among patients assigned single-agent everolimus (50%) compared with those assigned single-agent lenvatinib (79%) or the combination (71%).
The most common treatment-related adverse events were diarrhea (20%) among patients assigned the combination, proteinuria (19%) among patients assigned lenvatinib alone and anemia (12%) among patients assigned everolimus alone.
There were two deaths related to lenvatinib — a cerebral hemorrhage in the combination arm and a myocardial infraction in the lenvatinib monotherapy group.
Study limitations included the small sample size and no blinding. Additionally, although 18-month OS findings were notable (combination arm, 65%; 95% CI, 50-76; lenvatinib alone, 56%; 95% CI, 41-68; everolimus alone, 41%; 95% CI, 27-54), researchers noted the study was not powered for OS, meaning a significant follow-up is needed to observe any differences.
“In conclusion, the combination of lenvatinib plus everolimus resulted in a PFS benefit compared with everolimus, a standard therapy for renal cell carcinoma patients following progression on VEGF targeted drugs,” Motzer said. “Further study of lenvatinib is warranted in patients with advanced renal cell carcinoma.” – by Anthony SanFilippo
For more information:
Robert J. Motzer, MD, can be reached at motzerr@mskcc.org.
Disclosure: The study was funded by Eisai. Motzer reports consultant/advisory roles with and research funding from Bristol-Myers Squibb, Eisai, Genentech, GlaxoSmithKline, Novartis and Pfizer. Please see the full study for a list of the other researchers’ relevant financial disclosures.
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