Final Overall Survival Analysis of S1500: A Randomized, Phase II Study Comparing Sunitinib With Cabozantinib, Crizotinib, and Savolitinib in Advanced Papillary Renal Cell Carcinoma

<i>Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in</i> JCO <i>or elsewhere, for which the primary end point has already been reported.</i>Mesenchymal-epithelial transition (MET) signaling pathway plays a role in the pathogenesis of selected patients with papillary renal cell carcinoma (PRCC). In the phase II PAPMET trial (ClinicalTrials.gov identifier: NCT02761057), cabozantinib significantly prolonged progression-free survival and improved objective response rate compared with sunitinib in patients with advanced PRCC. Here, we present the final overall survival (OS) analysis. In this multicenter, randomized phase II, open-label trial, 147 patients with advanced PRCC who have received up to one previous therapy (excluding vascular endothelial growth factor-directed agents) were assigned to sunitinib, cabozantinib, crizotinib, or savolitinib. Ultimately, savolitinib and crizotinib arms were closed because of futility. With a median follow-up of 17.5 months, the median OS was 21.5 months (95% CI, 12.0 to 28.1) with cabozantinib and 17.3 months (95% CI, 12.8 to 21.8) with sunitinib (hazard ratio, 0.83; 95% CI, 0.51 to 1.36; <i>P</i> = .46). The OS landmark estimates for cabozantinib and sunitinib were 50% versus 39% at 24 months and 32% versus 28% at 36 months. In conclusion, we observed no significant difference in OS across treatment arms. Although cabozantinib represents a well-supported option for advanced PRCC, the lack of survival benefit underscores the need to develop novel therapies for this disease.

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Publication Details

Journal
Journal of Clinical Oncology
Published
2024-09-10
DOI
https://doi.org/10.1200/jco.24.00767
Citations
33
Primary Topic
Renal cell carcinoma treatment
Type
article
Field-Weighted Citation Impact
13.82
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article

Final Overall Survival Analysis of S1500: A Randomized, Phase II Study Comparing Sunitinib With Cabozantinib, Crizotinib, and Savolitinib in Advanced Papillary Renal Cell Carcinoma

Adebowale Adeniran, Maria Tretiakova, Ian M. Thompson, Daniel J. George et al.
33 citations
Journal of Clinical Oncology
Renal cell carcinoma treatment
13.82
article

Final Overall Survival Analysis of S1500: A Randomized, Phase II Study Comparing Sunitinib With Cabozantinib, Crizotinib, and Savolitinib in Advanced Papillary Renal Cell Carcinoma

Adebowale Adeniran, Maria Tretiakova, Ian M. Thompson, Daniel J. George, Brian Shuch, Catherine M. Tangen, Sumanta Kumar Pal, Melissa Plets, Ajjai Alva, Naomi B. Haas, Seth P. Lerner, Shuchi Gulati, Pedro Coelho Barata, Georg A. Bjarnason, Peter A. Humphrey, Vivek Narayan, Mark N. Stein, Ulka N. Vaishampayan, Primo N. Lara, Scott Cole, Abhishek Tripathi, Tian Zhang, Daniel Y.C. Heng
article en
33 citations

Abstract

<i>Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in</i> JCO <i>or elsewhere, for which the primary end point has already been reported.</i>Mesenchymal-epithelial transition (MET) signaling pathway plays a role in the pathogenesis of selected patients with papillary renal cell carcinoma (PRCC). In the phase II PAPMET trial (ClinicalTrials.gov identifier: NCT02761057), cabozantinib significantly prolonged progression-free survival and improved objective response rate compared with sunitinib in patients with advanced PRCC. Here, we present the final overall survival (OS) analysis. In this multicenter, randomized phase II, open-label trial, 147 patients with advanced PRCC who have received up to one previous therapy (excluding vascular endothelial growth factor-directed agents) were assigned to sunitinib, cabozantinib, crizotinib, or savolitinib. Ultimately, savolitinib and crizotinib arms were closed because of futility. With a median follow-up of 17.5 months, the median OS was 21.5 months (95% CI, 12.0 to 28.1) with cabozantinib and 17.3 months (95% CI, 12.8 to 21.8) with sunitinib (hazard ratio, 0.83; 95% CI, 0.51 to 1.36; <i>P</i> = .46). The OS landmark estimates for cabozantinib and sunitinib were 50% versus 39% at 24 months and 32% versus 28% at 36 months. In conclusion, we observed no significant difference in OS across treatment arms. Although cabozantinib represents a well-supported option for advanced PRCC, the lack of survival benefit underscores the need to develop novel therapies for this disease.

Journal of Clinical OncologyVol. 42(33)
Sunnybrook Health Science Centre (CA), Baylor College of Medicine (US), University of Washington (US), University of Michigan (US), Yale University (US), Fred Hutch Cancer Center (US), Medical Center Hospital (US), Oklahoma Cancer Specialists and Research Institute (US), City of Hope (US), Christus Santa Rosa Health System (US), University Hospitals Seidman Cancer Center (US), Duke Medical Center (US), UC Davis Comprehensive Cancer Center, Columbia University (US), University of Pennsylvania (US), University of California, Davis (US), The University of Texas Southwestern Medical Center (US)
Good health and well-being
Openalex Percentile: Top 1%
Renal cell carcinoma treatment
13.82
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