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.
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.
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.
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.
Cancer medicine. 2021 Mar 01 [Epub ahead of print]
Andrew L Laccetti, Benjamin Garmezy, Lianchun Xiao, Minas Economides, Aradhana Venkatesan, Jianjun Gao, Eric Jonasch, Paul Corn, Amado Zurita-Saavedra, Landon C Brown, Chester Kao, Emily N Kinsey, Rajan T Gupta, Michael R Harrison, Andrew J Armstrong, Daniel J George, Nizar Tannir, Pavlos Msaouel, Amishi Shah, Tian Zhang, Matthew T Campbell
Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Cancer Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA., Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA., Department of Internal Medicine, McGovern Medical School at UTHealth, Houston, TX, USA., Department of Radiology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA., Division of Medical Oncology, Department of Medicine, Duke University, Durham, NC, USA., Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC, USA.