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Everolimus Plus Bevacizumab Shows Activity in Advanced Non–Clear Cell Renal Cell Carcinoma

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Key Points

  • The combination of everolimus and bevacizumab showed activity in patients with advanced non–clear cell renal cell carcinoma characterized by papillary features.
  • The presence of ARID1A mutations, identified only in patients with papillary features, was associated with treatment benefit.

The combination of everolimus (Afinitor, Zortress) and bevacizumab (Avastin) was associated with clinical benefit in advanced non–clear cell renal cell carcinoma with a major papillary component, according to a single-center phase II trial reported by Voss et al in the Journal of Clinical Oncology.

In the trial, 35 evaluable treatment-naive patients received oral everolimus at 10 mg once daily plus bevacizumab 10 mg/kg intravenously every 2 weeks. Histologic subtypes were chromophobe (n = 5), papillary (n = 5), and medullary (n = 2) renal cell carcinoma and unclassified renal cell carcinoma (n = 23, 14 with papillary growth as a major component).

Clinical Benefit

Among 34 evaluable patients, median progression-free survival was 11.0 months, median overall survival was 18.5 months, and the objective response rate was 29%. Progression-free survival differed significantly according to histology (P < .001), and response rate was highest among patients with papillary (7 of 18) or chromophobe (two of five) features vs others (1 of 11). Among patients with non–clear cell renal cell carcinoma, presence vs absence of papillary features was associated with a better response rate (43% vs 11%), median progression-free survival (12.9 vs 1.9 months), and median overall survival (28.2 vs 9.3 months; P < .001 for all).

Correlative analysis showed that tumors from 5 of 14 patients with a major papillary component, including both papillary and non–clear cell renal cell carcinoma variants, had somatic mutations in ARID1A, with these alterations not being found in other renal cell carcinoma variants. Clinical benefit was observed in each of the five patients.

The investigators concluded: “The study suggests efficacy for this combination in patients with [non–clear cell renal cell carcinoma] characterized by papillary features. Distinct mutational profiles among [non–clear cell renal cell carcinomas] vary according to specific histology.”

The study was supported by Novartis International AG.

Martin H. Voss, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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