Combo treatment promising for metastatic renal cell carcinoma

29 Oct 2015

Patients of renal cell carcinoma benefited significantly when treated with a combination of lenvatinib with everolimus, a new phase 2 study reveals. The positive clinical results and the acceptable safety profile suggest that this drug combination can be used as a second-line treatment for this type of cancer.

Renal cell carcinoma (RCC) is the most common type of kidney cancer, responsible for over 90% of adult cases. The current ‘gold standard’ therapy for metastatic RCC is sequential treatment with single drugs that target the VEGF (vascular endothelial growth factor) and mTOR (mechanistic target of rapamycin) signaling pathways.

Studying the combination of lenvatinib with everolimus

A large, international team of clinicians and researchers led by Robert J. Motzer of Memorial Sloan-Kettering Cancer Center, New York, USA have conducted a Phase 2 trial of the combination in comparison with lenvatinib as a monotherapy, everolimus as a monotherapy or both agents together.

Lenvatinib is a multi-targeted kinase inhibitor that is active in the VEGF pathway and that is under investigation in several cancer types. A combination of this drug with everolimus has been shown to be more potent in a mouse model of renal cell carcinoma than either agent on its own. This drug combination has also been shown to have some efficacy and an acceptable safety profile in a Phase 1 trial in patients with the metastatic disease.

This randomized, open-label trial involved a total of 153 RCC patients from 37 centers in five countries, randomized in a 1:1:1 ratio to receive single-agent lenvatinib, single-agent everolimus or both agents together. All patients were diagnosed with the clear-cell type of renal cell carcinoma and had progressive disease after one treatment with a VEGF-directed therapy other than lenvatinib.

Patient demographics and disease characteristics were broadly similar between the three arms of the trial. The study treatment continued and patients were followed until disease progression, unacceptable adverse effects or withdrawal of patient consent.

CareAcross-ampoules

Treatment associated results and adverse effects

After analyzing the results, the research team announced that:

  • The median progression-free survival at the time of data cutoff was 14.6 months in the lenvatinib plus everolimus arm, 7.4 months in patients receiving lenvatinib alone and 5.5 months in those receiving everolimus alone.
  • The difference in progression-free survival between the combination therapy and everolimus arms reached statistical significance.
  • However, the difference between the combination therapy and lenvatinib arms was not significant.
  • Differences in overall survival did not reach statistical significance at the time of the original data cutoff, but an updated analysis found a significant difference in overall survival between the patients in the combination therapy arm (25.5 months) and those receiving everolimus alone (15.5 months).

Treatment-associated adverse effects were common but manageable in all arms, with the fewest in those patients who received everolimus only. The most commonly reported moderate or severe adverse effects were diarrhea in the combination therapy arm; proteinuria in the lenvatinib arm; and anemia in the everolimus arm.

The results of this Phase 2 trial therefore show that a combination of lenvatinib with everolimus can provide significant benefit as a second-line treatment in metastatic RCC, and the study authors suggest that further trials of lenvatinib as a single and combination agent are warranted in this tumor type.

Source: eCancer News

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