• Darren R Feldman, Yasser Ged, Chung-Han Lee, Andrea Knezevic, Ana M Molina, Ying-Bei Chen, Joshua Chaim, Devyn T Coskey, Samuel Murray, Satish K Tickoo, Victor E Reuter, Sujata Patil, Han Xiao, Jahan Aghalar, Arlyn J Apollo, Maria I Carlo, Robert J Motzer, and Martin H Voss.
• Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
• Cancer. 2020 Dec 15; 126 (24): 5247-5255.

BackgroundWe previously reported on a phase 2 study of everolimus plus bevacizumab across various nonclear cell renal cell carcinoma (nccRCC) histologies and observed encouraging activity among patients with papillary RCC (pRCC) and unclassified RCC (uRCC) with a major papillary component. We subsequently expanded the study to enroll additional patients with pRCC variants.MethodsEverolimus plus bevacizumab was administered at standard doses until disease progression or intolerance to therapy. The primary endpoint was the 6-month progression-free survival (PFS) rate; secondary endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Correlative analyses included next-generation sequencing (NGS) from tumor and germline across >341 genes of interest.ResultsIn addition to 19 patients with pRCC variants in the original cohort, 20 patients with similar features were enrolled on the expansion cohort (uRCC with papillary features [n = 24], pRCC [n = 14], and translocation-associated RCC with papillary features [n = 1]). Among 37 evaluable patients, the 6-month PFS rate was 78%, the median PFS was 13.7 months (95% CI, 10.8-16.4 months), and the ORR was 35%. With a median follow-up of 17.6 months, the median OS was 33.9 months (95% CI, 23.3-71.9). Tolerance was consistent with prior reports for everolimus plus bevacizumab. NGS results (n = 33) identified responses in patients with a wide spectrum of genomic alterations, including ARID1A, FH, and MET mutations.ConclusionThe expansion cohort results confirm robust activity of everolimus plus bevacizumab in metastatic pRCC variants, supporting this regimen as a standard option for this patient population.© 2020 American Cancer Society.

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