Open AccessCombination antiangiogenic tyrosine kinase inhibition and anti‐PD1 immunotherapy in metastatic renal cell carcinoma: A retrospective analysis of safety, tolerance, and clinical outcomes
Author(s) -
Laccetti Andrew L.,
Garmezy Benjamin,
Xiao Lianchun,
Economides Minas,
Venkatesan Aradhana,
Gao Jianjun,
Jonasch Eric,
Corn Paul,
ZuritaSaavedra Amado,
Brown Landon C.,
Kao Chester,
Kinsey Emily N.,
Gupta Rajan T.,
Harrison Michael R.,
Armstrong Andrew J.,
George Daniel J.,
Tannir Nizar,
Msaouel Pavlos,
Shah Amishi,
Zhang Tian,
Campbell Matthew T.
Publication year - 2021
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.3812
Subject(s) - medicine , nivolumab , ipilimumab , renal cell carcinoma , axitinib , pazopanib , cabozantinib , oncology , atezolizumab , progressive disease , adverse effect , response evaluation criteria in solid tumors , tyrosine kinase inhibitor , kidney cancer , cancer , surgery , immunotherapy , sunitinib , disease
Two separate antiangiogenic tyrosine kinase inhibitors (TKIs) and immunotherapy (IO) combinations are FDA‐approved as front‐line treatment for metastatic renal cell carcinoma (mRCC). Little is known about off‐protocol and post‐front‐line experience with combination TKI–IO approaches. Methods We conducted a retrospective analysis of mRCC patients who received combination TKI–IO post‐first‐line therapy between November 2015 and January 2019 at MD Anderson Cancer Center and Duke Cancer Institute. Chart review detailed patient characteristics, treatments, toxicity, and survival. Independent radiologists, blinded to clinical data, assessed best radiographic response using RECIST v1.1. Results We identified 48 mRCC patients for inclusion: median age 65 years, 75.0% clear cell histology, 68.8% IMDC intermediate risk, and median two prior systemic therapies. TKI–IO combinations included nivolumab–cabozantinib (N +C; 24 patients), nivolumab–pazopanib (N+P; 13), nivolumab–axitinib (6), nivolumab–lenvatinib (2), and nivolumab–ipilimumab–cabozantinib (3). The median progression‐free survival was 11.6 months and the median overall survival was not reached. Response data were available in 45 patients: complete response (CR; n = 3, 6.7%), partial response (PR; 20, 44.4%), stable disease (SD; 19, 42.2%), and progressive disease (3, 6.7%). Overall response rate was 51% and disease control rate (CR+PR+SD) was 93%. Only one patient had a grade ≥3 adverse event. Conclusion To our knowledge, this is the first case series reporting off‐label use of combination TKI–IO for mRCC. TKI–IO combinations, particularly N+P and N+C, are well tolerated and efficacious. Although further prospective research is essential, slow disease progression on IO or TKI monotherapy may be safely controlled with addition of either TKI or IO.