First-line immunotherapy of metastatic renal cell carcinoma: an updated network meta-analysis including triplet therapy

Takafumi Yanagisawa; Tatsushi Kawada; Kensuke Bekku; Ekaterina Laukhtina; Pawel Rajwa; Markus von Deimling; Marcin Chlosta; Fahad Quhal; Benjamin Pradere; Pierre I Karakiewicz; Keiichiro Mori; Takahiro Kimura; Shahrokh F Shariat; Manuela Schmidinger

doi:10.1111/bju.16336

First-line immunotherapy of metastatic renal cell carcinoma: an updated network meta-analysis including triplet therapy

BJU Int. 2024 Apr 24. doi: 10.1111/bju.16336. Online ahead of print.

Authors

Takafumi Yanagisawa^{1

2}, Tatsushi Kawada^{1

3}, Kensuke Bekku^{1

3}, Ekaterina Laukhtina¹, Pawel Rajwa^{1

4}, Markus von Deimling^{1

5}, Marcin Chlosta^{1

6}, Fahad Quhal^{1

7}, Benjamin Pradere^{1

8}, Pierre I Karakiewicz⁹, Keiichiro Mori^{1

2}, Takahiro Kimura², Shahrokh F Shariat^{1

10

11

12

13

14}, Manuela Schmidinger¹

Affiliations

¹ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
² Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
³ Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
⁴ Department of Urology, Medical University of Silesia, Zabrze, Poland.
⁵ Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁶ Clinic of Urology and Urological Oncology, Jagiellonian University, Krakow, Poland.
⁷ Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia.
⁸ Department of Urology, La Croix Du Sud Hospital, Quint Fonsegrives, France.
⁹ Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Québec, Canada.
¹⁰ Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria.
¹¹ Division of Urology, Department of Special Surgery, The University of Jordan, Amman, Jordan.
¹² Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹³ Department of Urology, Weill Cornell Medical College, New York, NY, USA.
¹⁴ Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.

PMID: 38659099
DOI: 10.1111/bju.16336

Abstract

Objective: To compare the differential efficacy of first-line immune checkpoint inhibitor (ICI)-based combined therapies among patients with intermediate- and poor-risk metastatic renal cell carcinoma (mRCC), as recently, the efficacy of triplet therapy comprising nivolumab plus ipilimumab plus cabozantinib has been published.

Patients and methods: Three databases were searched in December 2022 for randomised controlled trials (RCTs) analysing oncological outcomes in patients with mRCC treated with first-line ICI-based combined therapies. We performed network meta-analysis (NMA) to compare the outcomes, including progression-free survival (PFS) and objective response rates (ORRs), in patients with intermediate- and poor-risk mRCC; we also assessed treatment-related adverse events.

Results: Overall, seven RCTs were included in the meta-analyses and NMAs. Treatment ranking analysis revealed that pembrolizumab + lenvatinib (99%) had the highest likelihood of improved PFS, followed by nivolumab + cabozantinib (79%), and nivolumab + ipilimumab + cabozantinib (77%). Notably, compared to nivolumab + cabozantinib, adding ipilimumab to nivolumab + cabozantinib did not improve PFS (hazard ratio 1.02, 95% confidence interval 0.72-1.43). Regarding ORRs, treatment ranking analysis also revealed that pembrolizumab + lenvatinib had the highest likelihood of providing better ORRs (99.7%). The likelihoods of improved PFS and ORRs of pembrolizumab + lenvatinib were true in both International Metastatic RCC Database Consortium (IMDC) risk groups.

Conclusions: Our analyses confirmed the robust efficacy of pembrolizumab + lenvatinib as first-line treatment for patients with intermediate or poor IMDC risk mRCC. Triplet therapy did not result in superior efficacy. Considering both toxicity and the lack of mature overall survival data, triplet therapy should only be considered in selected patients.

Keywords: cabozantinib; immune checkpoint inhibitors; ipilimumab; metastasis; nivolumab; renal cell carcinoma.

Publication types

Review