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NEW YORK (Reuters Health) – First-line therapy with a combination of lenvatinib and everolimus had promising anticancer activity in patients with advanced non-clear-cell renal-cell carcinoma, with most patients seeing a decrease in tumor size and manageable side effects, in a phase-2 trial.

Non-clear-cell renal-cell carcinoma (nccRCC) makes up about 20% of RCC cases. Lenvatinib, a multitargeted tyrosine-kinase inhibitor (TKI), in combination with everolimus, an mTOR inhibitor, is approved for the treatment of advanced RCC after one prior anti-angiogenic therapy.

Dr. Thomas Hutson with Texas Oncology-Baylor Charles A. Sammons Cancer Center in Dallas and colleagues tested once-daily oral lenvatinib (18 mg) plus everolimus (5 mg) in 31 patients with unresectable advanced or metastatic nccRCC (20 papillary, nine chromophobe and two unclassified) and no prior anticancer therapy for advanced disease. Most patients were classified as intermediate or poor risk according to standard criteria.

The study start date was February 20, 2017. At the data cutoff date (July 17, 2019), cymbalta patient assistance program there were eight responses (three papillary, four chromophobe and one unclassified), for an overall objective response rate (ORR) of 26%, which “meets the prespecified threshold for statistical significance compared to historical controls of patients with advanced RCC,” the authors say.

They note that the ORR of 26% compares favorably to response rates reported for nccRCC patients treated with everolimus alone (9%). No ORRs have been reported to date for patients with nccRCC treated with lenvatinib alone. But the 26% ORR appears higher than that seen with other single-agent TKIs (with sunitinib, ORRs have ranged from 9% to 18%) and comparable to overall ORRs for patients receiving immunotherapy (ORRs ranging from 10% to 26%).

In the current study, the lenvatinib-everolimus combination was associated with an overall disease-control rate (DCR) of 84%; median progression-free survival was 9.2 months and median overall survival was 15.6 months.

No new safety signals emerged. The most common treatment-related side effects were fatigue (71%), diarrhea (58%), decreased appetite (55%), nausea (55%) and vomiting (52%).

In an editorial published with the study in European Urology, Dr. Daniel Geynisman and Dr. Elizabeth Plimack, with Fox Chase Cancer Center in Philadelphia, says the combination of lenvatinib and everolimus “can now be considered an option for nccRCC patients, in particular those with chRCC.”

“There has undoubtedly been progress in the evaluation and management of nccRCC, but much remains to be done. We expect that the next decade will lead to more precise molecular classification and biomarker-directed management of this rare and diverse group of patients,” they write.

Funding for the study was provided by Eisai Inc and Merck Sharp and Dohme Corp. Several authors disclosed financial relationships with the companies.

SOURCE: https://bit.ly/3f7V2xH and https://bit.ly/3vP9Bx0 European Urology, online May 7, 2021.

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