medwireNews: Previously untreated patients with advanced non-clear cell renal cell carcinoma (nccRCC) could benefit from treatment with lenvatinib plus everolimus, suggests a phase 2 study.
The combination of the multitargeted tyrosine kinase inhibitor lenvatinib and the mTOR inhibitor everolimus demonstrated “encouraging anticancer activity” in this patient population and “[t]he safety profile was consistent with the established profile of the study-drug combination,” say the investigators.
These findings indicate that the dual regimen “is worthy of future study in patients with nccRCC,” they add.
Among the 31 participants with locally advanced or metastatic nccRCC, the most common histologic subtype was papillary, observed in 65% of patients, followed by chromophobe and unclassified, in 29% and 6%, respectively.
Treatment with lenvatinib 18 mg/day alongside everolimus 5 mg/day achieved an investigator-assessed objective response rate (ORR) of 26%, where all responses were partial. An additional 58% of patients had stable disease, which was maintained for at least 23 weeks in 35%, giving disease control and clinical benefit rates of 84% and 61%, respectively.
“While no confirmed complete responses were observed in this study, partial responses were observed in patients across all histological subtypes enrolled,” report the researchers. Specifically, the ORRs were 15% and 44% in the papillary and chromophobe subgroups, respectively, and there was one response among the two patients with unclassified disease.
Median progression-free survival in the full cohort was 9.2 months and ranged from 9.2 months for the papillary subtype to 13.1 months for chromophobe disease. The corresponding durations for median overall survival were 15.6 months, 11.7 months, and unreached.
Thomas Hutson (Texas Oncology–Baylor Charles A Sammons Cancer Center, Dallas, USA) and collaborators report in European Urology that grade 3 or worse treatment-emergent adverse events (TEAEs) occurred in 68% of participants.
The same proportion of patients required a dose interruption of lenvatinib and/or everolimus due to TEAEs, while 45% needed a dose reduction of lenvatinib and 32% discontinued treatment. Three TEAEs were fatal but none were deemed related to study treatment.
Discussing the results, the investigators highlight that “[t]he observed overall ORR of 26% in this study meets the prespecified threshold for statistical significance compared to historical controls of patients with advanced RCC.”
And they conclude: “Given the pathways involved in nccRCC and the mechanisms of action of lenvatinib and everolimus, further applied development of these combined agents and combinations of agents with other mechanisms, such as anti–PD-1/L1 plus anti–CTLA4 antibodies or anti–PD-1/L agents plus VEGF inhibitors remain of interest.”
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