Angiogenesis has been recognized as the most important factor for tumor invasion, proliferation, and progression in metastatic renal cell carcinoma (mRCC). However, few clinical data are available regarding the efficacy of cabozantinib following immunotherapy.
To describe the outcome of cabozantinib in patients previously treated with immunotherapy.
Patients and methods
Patients with mRCC who received cabozantinib immediately after nivolumab were included. The primary endpoint was to assess the outcome in terms of efficacy and activity.
Eighty-four mRCC patients met the criteria to be included in the final analysis. After a median follow-up of 9.4 months, median overall survival was 17.3 months. According to the IMDC criteria, the rates of patients alive at 12 months in the good, intermediate, and poor prognostic groups were 100%, 74%, and 33%, respectively (p < 0.001). The median progression-free survival (PFS) was 11.5 months (95% CI 8.3–14.7); no difference was found based on duration of previous first-line therapy or nivolumab PFS. The overall response rate was 52%, stable disease was found as the best response in 25.3% and progressive disease in 22.7% of patients. Among the 35 patients with progressive disease on nivolumab, 26 (74.3%) patients showed complete/partial response or stable disease with cabozantinib as best response after nivolumab. The major limitations of this study are the retrospective nature and the short follow-up.
Cabozantinib was shown to be effective and active in patients previously receiving immune checkpoint inhibitors. Therefore, cabozantinib can be considered a valid therapeutic option for previously treated mRCC patients, irrespective of the type and duration of prior therapies.
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Choueiri TK, Motzer RJ. Systemic therapy for metastatic renal-cell carcinoma. N Engl J Med. 2017;376:354–66.
Choueiri TK, Escudier B, Powles T, Tannir NM, Mainwaring PN, Rini BI, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016;17:917–27.
Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373:1803–13.
Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378:1277–90.
Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380:1116–27.
Motzer RJ, Penkov K, Haanen J, Rini B, Albiges L, Campbell MT, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380:1103–11157.
Nadal R, Amin A, Geynisman DM, Voss MH, Weinstock M, Doyle J, et al. Safety and clinical activity of vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitors after programmed cell death 1 inhibitor treatment in patients with metastatic clear cell renal cell carcinoma. Ann Oncol. 2016;27:1304–11.
Albiges L, Fay AP, Xie W, Krajewski K, McDermott DF, Heng DY, et al. Efficacy of targeted therapies after PD-1/PD-L1 blockade in metastatic renal cell carcinoma. Eur J Cancer. 2015;51:2580–6.
Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol. 2009;27:5794–9.
Powles T, Motzer RJ, Escudier B, Pal S, Kollmannsberger C, Pikiel J, et al. Outcomes based on prior therapy in the phase 3 METEOR trial of cabozantinib versus everolimus in advanced renal cell carcinoma. Br J Cancer. 2018;119:663–9.
McGregor BA, Lalani A, Xie W, Steinharter JA, Martini DJ, Nuzzo PV, et al. Activity of cabozantinib (cabo) after PD-1/PD-L1 immune checkpoint blockade (ICB) in metastatic clear cell renal cell carcinoma (mccRCC). Ann Oncol. 2018;29(suppl_8):3iii303–viii331. https://doi.org/10.1093/annonc/mdy283.
Derosa L, Rouche JA, Colomba E, Baciarello G, Routy B, Albiges L, et al. Efficacy of cabozantinib (C) after PD-1/PD-L1 checkpoint inhibitors in metastatic Renal Cell Carcinoma (mRCC): the Gustave Roussy experience. Ann Oncol. 2017;28(suppl_5):v295–v329. https://doi.org/10.1093/annonc/mdx371.
Auvray M, Auclin E, Barthelemy P, Bono P, Kellokumpu-Lehtinen P, Gross-Goupil M, et al. Second-line targeted therapies after nivolumab-ipilimumab failure in metastatic renal cell carcinoma. Eur J Cancer. 2019;108:33–40.
Jenkins RW, Barbie DA, Flahert KT. Mechanisms of resistance to immune checkpoint inhibitors. Br J Cancer. 2018;118:9–16.
Kwilas AR, Ardiani A, Donahue RN, Aftab DT, Hodge JW. Dual effects of a targeted small-molecule inhibitor (cabozantinib) on immune-mediated killing of tumor cells and immune tumor microenvironment permissiveness when combined with a cancer vaccine. J Transl Med. 2014;12:294.
The authors would like to thank Dr. Franziska Michaela Lohmeyer for help with language editing of the manuscript.
No external funding was used in the preparation of this article.
Conflict of interest
R. Iacovelli served as consultant for Ipsen; Pfizer; Novartis; BMS, MSD, Janssen. G. Procopio served as consultant for Bayer, BMS, Ipsen, Janssen, MSD, Novartis, Pfizer. Conflict of interest/Competing interests: Roberto Iacovelli served as consultant for Ipsen; Pfizer; Novartis; BMS, MSD, Janssen. Giuseppe Procopio served as consultant for Bayer, BMS, Ipsen, Janssen, MSD, Novartis, Pfizer. Chiara Ciccarese, Gaetano Facchini, Michele Milella, Federica Urbano, Umberto Basso, Ugo De Giorgi, Roberto Sabbatini, Daniele Santini, Rossana Berardi, Matteo Santoni, Sergio Bracarda, Francesco Massari, Cristina Masini, Michele De Tursi, Riccardo Ricotta, Sebastiano Buti, Fable Zustovich, Pierangela Sepe, Sabrina Rossetti, Marco Maruzzo, Enrico Cortesi, and Giampaolo Tortora declare that they have no conflicts of interest that might be relevant to the contents of this article.
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Iacovelli, R., Ciccarese, C., Facchini, G. et al. Cabozantinib After a Previous Immune Checkpoint Inhibitor in Metastatic Renal Cell Carcinoma: A Retrospective Multi-Institutional Analysis. Targ Oncol 15, 495–501 (2020). https://doi.org/10.1007/s11523-020-00732-y