Outcomes With First-Line PD-1/PD-L1 Inhibitor Monotherapy for Metastatic Renal Cell Carcinoma (mRCC): A Multi-Institutional Cohort

• Type of Material: Article
• Authors: Pedro Barata, Tulane University; Whitley Hatton, Tulane University; Arpita Desai, University of California San Francisco; Vadim Koshkin, University of California San Francisco; Ellen Jaeger, Tulane University; Charlotte Manogue, Tulane University; Patrick Cotogno, Tulane University; Malcolm Light, Tulane University; Brian Lewis, Tulane University; Jodi Layton, Tulane University; Oliver Sartor, Tulane University; Arnab Basu, University of Alabama Birmingham; Deepak Kilari, Wisconsin Cancer Center; Hamid Emamekhoo, University of Wisconsin; Mehmet Bilen, Emory University
• Language: English
• Date: 2020-10-22
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Barata, Hatton, Desai, Koshkin, Jaeger, Manogue, Cotogno, Light, Lewis, Layton, Sartor, Basu, Kilari, Emamekhoo and Bilen.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fonc.2020.581189
• Title of Journal or Parent Work: FRONTIERS IN ONCOLOGY
• Volume: 10
• Start Page: 581189
• End Page: 581189
• Grant/Funding Information: This work was supported by LA CaTS Center Grant Number U54 GM104940.
• Keywords: immunotherapy; Life Sciences & Biomedicine; NIVOLUMAB; PD-1; Oncology; monotherapy; Science & Technology; first-line treatment; metastatic renal cell carcinoma; PD-L1 inhibitor
• Research Categories: Health Sciences, Oncology; Health Sciences, Rehabilitation and Therapy; Biology, Cell

Abstract

Introduction: The treatment landscape of metastatic renal cell carcinoma has advanced significantly with the approval of combination regimens containing an immune checkpoint inhibitor (ICI) for patients with treatment-naïve disease. Little information is available regarding the activity of single-agent ICIs for patients with previously untreated mRCC not enrolled in clinical trials. Methods: This retrospective, multicenter cohort included consecutive treatment-naïve mRCC patients from six institutions in the United States who received ≥1 dose of an ICI outside a clinical trial, between June 2017 and October 2019. Descriptive statistics were used to analyze outcomes including objective best response rate (ORR), progression-free survival (PFS), and tolerability. Results: The final analysis included 27 patients, 70% men, median age 64 years (range 42–92), 67% Caucasian, and 33% with ECOG 2 or 3 at baseline. Most patients had intermediate risk (85%, IMDC) with clear cell (56%), papillary (26%), unclassified (11%), chromophobe (4%), and translocation (4%) RCC. All patients had evidence of metastatic disease involving the lungs (59%), lymph node (41%), CNS (19%), liver (11%), adrenal gland (11%), and bone (11%). The median time on ICI was 3.1 (0.1–26.8) months, and the median PFS was 6.3 (95% CI, 0–18.6) months. Among the 21 patients with an evaluable response, the best ORR was 33%, including two complete responses and five partial responses. The ORR was 29% (n = 1 complete response, n = 5 partial response) in clear cell and 5% (n = 1 complete response) in non-clear cell RCC. Adverse events (AEs) of any cause were reported in 37% and included fatigue (11%), dermatitis (11%), diarrhea (7%), and shortness of breath (7%). Significant AEs (30%) included shortness of breath (7%), acute kidney injury (4%), dermatitis (4%), Clostridium difficile infection (4%), cerebrovascular accident (4%), and fatigue (7%). Three patients discontinued therapy due to grade 4 AEs. Conclusions: In this multi-institutional case series, single-agent ICI demonstrated objective responses and was well tolerated in a heterogeneous treatment-naïve mRCC cohort. ICI monotherapy is not the standard of care for patients with mRCC, and further investigation is necessary to explore predictive biomarkers for optimal treatment selection in this setting.