Salvage lenvatinib/everolimus combination therapy after immune checkpoint inhibitor and VEGFR tyrosine kinase inhibitor for metastatic renal cell carcinoma

Frontiers in Oncology

Oncology

Christopher Kwok¹  Megan Hinkley¹  Sarah P. Psutka²  Yuanquan Yang³  Claire Verschraegen³  Adam Khorasanchi³  Yajing Yang³  Ming Yin³  Shawn Dason⁴  Debasish Sundi⁴  Delaney Orcutt⁵  Evan E. Gross⁵ 

[1] Department of Pharmacy, The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States;Department of Urology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA, United States;Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States;Division of Urologic Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States;The University of Washington School of Medicine, Seattle, WA, United States;

关键词: lenvatinib;    everolimus;    immune checkpoint inhibitor;    VEGFR tyrosine kinase inhibitor;    renal cell carcinoma;    retrospective review;   

DOI  :  10.3389/fonc.2023.1231831

 received in 2023-05-31, accepted in 2023-07-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundThe optimal treatment for metastatic renal cell carcinoma (mRCC) patients who have progressed after both immune checkpoint inhibitor (ICI) and VEGFR tyrosine kinase inhibitor (TKI) remains uncertain. Lenvatinib and everolimus (LE) are frequently used in combination as salvage therapy because of their different antitumor mechanisms, but efficacy and toxicity data in this setting are lacking.MethodsWe retrospectively reviewed charts from two academic centers for 71 adult mRCC patients who received LE after prior ICI and TKI exposure. We evaluated patient demographics, histology, International mRCC Database Consortium (IMDC) risk group, treatment history, and toxicity details. Outcomes of interest included objective response rate (ORR), time to treatment failure (TTF), overall survival (OS), ≥grade 3 toxicities, and schedule or dosage changes, which were evaluated using descriptive statistics, chi-square test, Cox proportional hazards model, and the Kaplan–Meier method.ResultsThe median age was 64 (range 31–84). Most patients had clear cell histology (84.5%) and had undergone nephrectomy (80.3%). IMDC risks were favorable (19.7%), intermediate (int) (66.2%), poor (11.3%), and unknown (2.8%). The average ORR was 26.8%, while the median TTF was 5.5 months (95% confidence interval [CI], 3.5–7.6) and the median OS was 9 months (95% CI, 7.6–12.9). Intermediate and poor IMDC risks were independently associated with a significantly worse TTF compared to favorable risk (hazard ratio (HR), 3.03, 95% CI, 1.18–7.79), as was ≥4L treatment vs. 2L/3L treatment (HR, 2.02, 95% CI, 1.08–3.8). Of the 71 patients, 57.7% had ≥grade 3 adverse events, 60% had treatment interruption, 44.3% had dose reduction, and 21% stopped treatment due to intolerance.ConclusionsLE therapy is feasible but has modest efficacies following ICI/TKI treatment. Patients with favorable risk or treated earlier may have a better treatment response. These observations need to be confirmed in prospective studies.

【 授权许可】

Unknown   
Copyright © 2023 Kwok, Khorasanchi, Psutka, Hinkley, Dason, Sundi, Yang, Yang, Verschraegen, Gross, Orcutt and Yin