@article{f25ef020e8de47da88e0e67dab2243d3,
title = "Everolimus plus bevacizumab is an effective first-line treatment for patients with advanced papillary variant renal cell carcinoma: Final results from a phase II trial",
abstract = "Background: We 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. Methods: Everolimus 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. Results: In 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. Conclusion: The 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.",
keywords = "RCC, bevacizumab, everolimus, genomics, papillary RCC",
author = "Feldman, {Darren R.} and Yasser Ged and Lee, {Chung Han} and Andrea Knezevic and Molina, {Ana M.} and Chen, {Ying Bei} and Joshua Chaim and Coskey, {Devyn T.} and Samuel Murray and Tickoo, {Satish K.} and Reuter, {Victor E.} and Sujata Patil and Han Xiao and Jahan Aghalar and Apollo, {Arlyn J.} and Carlo, {Maria I.} and Motzer, {Robert J.} and Voss, {Martin H.}",
note = "Funding Information: This investigator-initiated trial was supported by Novartis International AG (Basel, Switzerland), the Kidney Cancer Foundation, and the National Institutes of Health (Cancer Center Support Grant P30 CA008748). Darren R. Feldman has received research support from Novartis, Astellas, Decibel, and Seattle Genetics. Chung-Han Lee has received personal fees from Amgen, Bristol-Myers Squibb, Exelixis, Eisai, Merck, Pfizer, EMD Serono, and Intellisphere; grants from Bristol-Myers Squibb, Calithera, Exelixis, Eisai, Merck, Pfizer, and Eli Lilly; and nonfinancial support from Calithera and Eisai. Ana M. Molina has received personal fees from Exelixis and Eisai. Satish K. Tickoo has received grant support from Null. Victor E. Reuter has received personal fees from Cepheid. Jahan Aghalar has received personal fees from Janssen, Bayer, Sanofi, and EMD Serono. Maria I. Carlo has received personal fees from Pfizer. Robert Motzer has received personal fees from Pfizer, Eisai, Exelixis, Novartis, Genentech/Roche, Merck, Incyte, and Eli Lilly; grants from Pfizer, Eisai, Novartis, Bristol-Myers Squibb, Genentech/Roche, and GlaxoSmithKline; and travel/accommodation expenses from Bristol-Myers Squibb. Martin H. Voss has received grants from Bristol-Myers Squibb, Genentech/Roche, and Pfizer; has received nonfinancial support from AstraZeneca/Medimmune; has received personal fees from Novartis, Pfizer, Exelixis, Eisai, Corvus, Calithera, and Merck; has received travel/accommodation expenses from Eisai, Novartis, and Takeda; and has been a consultant/advisory board member for Alexion Pharmaceuticals, Bayer, Calithera Biosciences, Corvus Pharmaceuticals, Exelixis, Eisai, GlaxoSmithKline, Natera, Novartis, OnQuality Pharmaceuticals, and Pfizer. The other authors made no disclosures. Funding Information: This investigator‐initiated trial was supported by Novartis International AG (Basel, Switzerland), the Kidney Cancer Foundation, and the National Institutes of Health (Cancer Center Support Grant P30 CA008748). Publisher Copyright: {\textcopyright} 2020 American Cancer Society",
year = "2020",
month = dec,
day = "15",
doi = "10.1002/cncr.33148",
language = "English (US)",
volume = "126",
pages = "5247--5255",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "24",
}