Outcomes of patients with advanced non-clear cell renal cell carcinoma treated with first-line immune checkpoint inhibitor therapy

Jeffrey Graham; John Connor Wells; Shaan Dudani; Chun L Gan; Frede Donskov; Jae-Lyun Lee; Christian K Kollmannsberger; Luis Meza; Benoit Beuselinck; Aaron Hansen; Scott A North; Georg A Bjarnason; Nicolas Sayegh; Ravindran Kanesvaran; Lori A Wood; Sebastien J Hotte; Rana R McKay; Toni K Choueiri; Daniel Y C Heng

doi:10.1016/j.ejca.2022.05.002

Outcomes of patients with advanced non-clear cell renal cell carcinoma treated with first-line immune checkpoint inhibitor therapy

Eur J Cancer. 2022 Aug:171:124-132. doi: 10.1016/j.ejca.2022.05.002. Epub 2022 Jun 16.

Authors

Jeffrey Graham¹, John Connor Wells², Shaan Dudani³, Chun L Gan⁴, Frede Donskov⁵, Jae-Lyun Lee⁶, Christian K Kollmannsberger⁷, Luis Meza⁸, Benoit Beuselinck⁹, Aaron Hansen¹⁰, Scott A North¹¹, Georg A Bjarnason¹², Nicolas Sayegh¹³, Ravindran Kanesvaran¹⁴, Lori A Wood¹⁵, Sebastien J Hotte¹⁶, Rana R McKay¹⁷, Toni K Choueiri¹⁸, Daniel Y C Heng⁴

Affiliations

¹ University of Manitoba, Winnipeg, MB, Canada; CancerCare Manitoba Research Institute, CancerCare Manitoba, Winnipeg, MB, Canada. Electronic address: jgraham9@cancercare.mb.ca.
² Queen's University, Kingston, ON, Canada.
³ Division of Oncology/Hematology, William Osler Health System, Brampton, ON, Canada.
⁴ University of Calgary, Calgary, Alberta, Canada.
⁵ Aarhus University Hospital, Aarhus, Denmark.
⁶ Asan Medical Center and University of Ulsan College of Medicine, Seoul, South Korea.
⁷ BC Cancer-Vancouver Centre, Vancouver, BC, Canada.
⁸ Department of Medical Oncology and Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
⁹ Leuven Cancer Institute, Universitaire Ziekenhuizen, Leuven, Belgium.
¹⁰ Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
¹¹ University of Alberta Cross Cancer Institute, Edmonton, AB, Canada.
¹² Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada.
¹³ Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
¹⁴ National Cancer Centre Singapore, Singapore.
¹⁵ Dalhousie University, Halifax, NS, Canada.
¹⁶ Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada.
¹⁷ University of California San Diego, Moores Cancer Center, La Jolla, CA, USA.
¹⁸ Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.

PMID: 35717820
DOI: 10.1016/j.ejca.2022.05.002

Abstract

Background: Immune checkpoint inhibitors (ICI) have demonstrated impressive activity in metastatic clear-cell renal cell carcinoma (ccRCC) and have become standard treatment options for patients with advanced disease. Data supporting the effectiveness of ICI-based therapy in advanced non-clear cell RCC (nccRCC) is more limited.

Methods: We performed a retrospective analysis using the International Metastatic RCC Database Consortium (IMDC) to evaluate the outcomes of patients with advanced nccRCC. Patients were classified into three groups based on first-line therapy: ICI-based therapy (monotherapy or combination), vascular endothelial growth factor (VEGF) inhibitor monotherapy, or mammalian target of rapamycin (mTOR) inhibitor monotherapy. The primary outcome was overall survival (OS). Secondary outcomes were time to treatment failure (TTF) and objective response rate (ORR). We used the Kaplan-Meier method to compare OS and TTF between treatment groups and Cox proportional hazards models to adjust for prognostic covariates.

Results: We identified a total of 1145 patients with metastatic nccRCC. The most common subtype was papillary RCC (54.9%). For first-line therapy, 74.3% received VEGF monotherapy, 15% received mTOR monotherapy, and 10.7% received ICI-based therapy. Median OS in the ICI group was 28.6 months, versus 16.4 months in the VEGF group and 12.2 months in the mTOR group. Median TTF in the ICI group was 6.9 months, versus 5.0 months in the VEGF group and 3.9 months in the mTOR group. ORR was 27.2% in the ICI group, 14.5% in the VEGF group, and 9% in the mTOR group. After adjusting for the IMDC risk group, histological subtype, and age, the hazard ratio for OS was 0.57 (95% CI 0.42-0.78, p < 0.0001) for ICI versus VEGF and 0.50 (95% CI 0.36-0.71, p < 0.0001) for ICI versus mTOR.

Conclusions: In advanced nccRCC, first-line ICI-based treatment appears to be associated with improved OS compared to VEGF and mTOR targeted therapy. These results should be confirmed in prospective randomised trials.

Keywords: Immune checkpoint inhibitor; Immunotherapy; Kidney cancer; Non-clear cell RCC; Renal cell carcinoma; Variant histology RCC.

MeSH terms

Angiogenesis Inhibitors / therapeutic use
Carcinoma, Renal Cell* / pathology
Humans
Immune Checkpoint Inhibitors / therapeutic use
Kidney Neoplasms* / pathology
Retrospective Studies
TOR Serine-Threonine Kinases
Treatment Outcome
Vascular Endothelial Growth Factor A

Substances

Angiogenesis Inhibitors
Immune Checkpoint Inhibitors
Vascular Endothelial Growth Factor A
TOR Serine-Threonine Kinases

Supplementary concepts

Clear-cell metastatic renal cell carcinoma