Impact of smoking status on clinical outcomes in patients with metastatic renal cell carcinoma treated with first-line immune checkpoint inhibitor-based regimens

Eddy Saad; Georges Gebrael; Karl Semaan; Marc Eid; Renée Maria Saliby; Chris Labaki; Nicolas Sayegh; J Connor Wells; Kosuke Takemura; Matthew Scott Ernst; Audreylie Lemelin; Naveen S Basappa; Lori A Wood; Thomas Powles; D Scott Ernst; Aly-Khan A Lalani; Neeraj Agarwal; Wanling Xie; Daniel Y C Heng; Toni K Choueiri

doi:10.1093/oncolo/oyae072

Impact of smoking status on clinical outcomes in patients with metastatic renal cell carcinoma treated with first-line immune checkpoint inhibitor-based regimens

Oncologist. 2024 Apr 17:oyae072. doi: 10.1093/oncolo/oyae072. Online ahead of print.

Authors

Eddy Saad¹, Georges Gebrael², Karl Semaan¹, Marc Eid¹, Renée Maria Saliby¹, Chris Labaki^{1

3}, Nicolas Sayegh^{2

4}, J Connor Wells⁵, Kosuke Takemura⁶, Matthew Scott Ernst⁷, Audreylie Lemelin⁷, Naveen S Basappa⁸, Lori A Wood⁹, Thomas Powles¹⁰, D Scott Ernst¹¹, Aly-Khan A Lalani¹², Neeraj Agarwal², Wanling Xie¹, Daniel Y C Heng⁷, Toni K Choueiri¹

Affiliations

¹ Dana-Farber Cancer Institute, Boston, MA, United States.
² Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, United States.
³ Beth Israel Deaconess Medical Center, Boston, MA, United States.
⁴ UT Southwestern Medical Center, Dallas, TX, United States.
⁵ BC Cancer Agency, Vancouver, Canada.
⁶ Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
⁷ Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada.
⁸ Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada.
⁹ Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, NS, Canada.
¹⁰ Experimental Cancer Medicine Centre, Barts Cancer Institute, St. Bartholomew's Hospital, Queen Mary University of London, London, United Kingdom.
¹¹ Department of Oncology, Western University, London, ON, Canada.
¹² Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada.

PMID: 38630540
DOI: 10.1093/oncolo/oyae072

Abstract

Background: Current tobacco smoking is independently associated with decreased overall survival (OS) among patients with metastatic renal cell carcinoma (mRCC) treated with targeted monotherapy (VEGF-TKI). Herein, we assess the influence of smoking status on the outcomes of patients with mRCC treated with the current first-line standard of care of immune checkpoint inhibitor (ICI)-based regimens.

Materials and methods: Real-world data from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were collected retrospectively. Patients with mRCC who received either dual ICI therapy or ICI with VEGF-TKI in the first-line setting were included and were categorized as current, former, or nonsmokers. The primary outcomes were OS, time to treatment failure (TTF), and objective response rate (ORR). OS and TTF were compared between groups using the log-rank test and multivariable Cox regression models. ORR was assessed between the 3 groups using a multivariable logistic regression model.

Results: A total of 989 eligible patients were included in the analysis, with 438 (44.3%) nonsmokers, 415 (42%) former, and 136 (13.7%) current smokers. Former smokers were older and included more males, while other baseline characteristics were comparable between groups. Median follow-up for OS was 21.2 months. In the univariate analysis, a significant difference between groups was observed for OS (P = .027) but not for TTF (P = .9), with current smokers having the worse 2-year OS rate (62.8% vs 70.8% and 73.1% in never and former smokers, respectively). After adjusting for potential confounders, no significant differences in OS or TTF were observed among the 3 groups. However, former smokers demonstrated a higher ORR compared to never smokers (OR 1.45, P = .02).

Conclusion: Smoking status does not appear to independently influence the clinical outcomes to first-line ICI-based regimens in patients with mRCC. Nonetheless, patient counseling on tobacco cessation remains a crucial aspect of managing patients with mRCC, as it significantly reduces all-cause mortality.

Keywords: immune checkpoint inhibitors; immunotherapy; kidney cancer; renal cell carcinoma; smoking.