Immune checkpoint inhibitor/tyrosine kinase inhibitor (ICI/TKI) combinations are a new standard of care for the initial treatment of metastatic renal cell carcinoma (mRCC). Their efficacy and toxicity beyond the first-line setting remain poorly defined.
We retrospectively reviewed charts for 85 adults with mRCC of any histology receiving combination of ICI/TKI in any line of treatment at two academic centers as of 05/01/2020. We collected clinical, pathological, and treatment-related variables. Outcomes including objective response rate (ORR), progression-free survival (PFS), and toxicity were analyzed via descriptive statistics and the Kaplan-Meier method.
Patients received pembrolizumab, nivolumab, avelumab, or nivolumab-ipilimumab, with concurrent use of sunitinib, axitinib, pazopanib, lenvatinib, or cabozantinib. Thirty-three patients received first-line ICI/TKI therapy, while 52 received ≥ second-line ICI/TKI. The efficacy of ICI/TKI therapy decreased with increasing lines of treatment (ORR: 56.7%, 37.5%, 21.4%, and 21%; median PFS [mPFS]: 15.2, 14.2, 10.1, and 6.8 months, for first, second, third, and ≥ fourth line therapy, respectively). In the ≥ second-line setting, ICI/TKI was most useful in patients who received ICI only, with an ORR of 50% and a mPFS of 9.1 months. Efficacy was limited in patients who received both TKI and ICI previously, with an ORR of 20% and a mPFS of 5.5 months. Overall, ≥ second-line ICI/TKI was tolerable with 25 of 52 (52%) patients developing grade ≥3 adverse events.
ICI/TKI combination therapy is feasible and safe beyond the first-line setting. Prior treatment history appears to impact efficacy but has a lesser effect on safety/tolerability.
Cancer medicine. 2022 Mar 18 [Epub ahead of print]
Yuanquan Yang, Sarah P Psutka, Anish B Parikh, Mingjia Li, Katharine Collier, Abdul Miah, Sherry V Mori, Megan Hinkley, Scott S Tykodi, Evan Hall, John A Thompson, Ming Yin
Genitourinary Oncology Section, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center - James Cancer Hospital, Columbus, Ohio, USA., Department of Urology, University of Washington School of Medicine, Seattle, Washington, USA., Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA., Division of Medical Oncology, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington, USA.