The comparative efficacy and health-related quality of life (HRQoL) outcomes of nivolumab plus cabozantinib versus pembrolizumab plus axitinib as first-line treatments for advanced renal cell carcinoma (aRCC) have not been assessed in head-to-head trials.
To assess the efficacy and HRQoL outcomes of nivolumab plus cabozantinib versus pembrolizumab plus axitinib.
Patient-level data for nivolumab plus cabozantinib from the CheckMate 9ER trial and published data for pembrolizumab plus axitinib from the KEYNOTE-426 trial were used. CheckMate 9ER data were reweighted to match the key baseline characteristics as reported in KEYNOTE-426.
Nivolumab (240 mg every 2 wk) plus cabozantinib (40 mg once daily) and pembrolizumab (200 mg every 3 wk) plus axitinib (5 mg twice daily, initially).
Hazard ratios (HRs) for progression-free survival (PFS), duration of response, overall survival (OS), and deterioration in HRQoL were assessed using weighted Cox proportional-hazard models, with sunitinib as a common anchor. Objective response rates (ORRs) and changes in HRQoL scores from baseline were assessed as difference-in-differences for the two treatments relative to sunitinib.
After balancing patient characteristics between the trials, nivolumab plus cabozantinib was associated with significantly improved PFS (HR [95% confidence interval {CI}] 0.70 [0.53-0.93]; p = 0.01) and a significantly decreased risk of confirmed deterioration in HRQoL (Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-related Symptoms: HR [95% CI] 0.48 [0.34-0.69]) versus pembrolizumab plus axitinib. OS was similar between treatments (HR [95% CI] 0.99 [0.67-1.44]; p = 0.94). Nivolumab plus cabozantinib was associated with numerically greater ORRs (difference-in-difference [95% CI] 8.4% [-1.7 to 18.4]; p = 0.10) and longer duration of response (HR [95% CI] 0.79 [0.47-1.31]; p = 0.36) than pembrolizumab plus axitinib. Comparative studies using data with a longer duration of follow-up are warranted.
Nivolumab plus cabozantinib significantly improved PFS and HRQoL compared with pembrolizumab plus axitinib as first-line treatment for aRCC.
This study was conducted to indirectly compare the results of two immunotherapy-based combinations-nivolumab plus cabozantinib versus pembrolizumab plus axitinib-for patients who have not received any treatment for advanced renal cell carcinoma. Patients who received nivolumab plus cabozantinib had a significant improvement in the length of time without worsening of their disease and in their perceived physical and mental health compared with pembrolizumab plus axitinib; patients remained alive for a similar length of time from the start of either treatment. This analysis further adds to our current knowledge of the relative benefits of these two treatment regimens and will help with physician and patient treatment decisions.
European urology oncology. 2023 Feb 24 [Epub ahead of print]
Bradley McGregor, Daniel M Geynisman, Mauricio Burotto, Cristina Suárez, Maria T Bourlon, Pedro C Barata, Shuchi Gulati, Stephen Huo, Flavia Ejzykowicz, Steven I Blum, Viviana Del Tejo, Melissa Hamilton, Jessica R May, Ella X Du, Aozhou Wu, Pavol Kral, Cristina Ivanescu, Andi Chin, Keith A Betts, Chung-Han Lee, Toni K Choueiri, David Cella, Camillo Porta
The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA., Bradford Hill Clinical Research Center, Santiago, Chile., Department of Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain., Hematology-Oncology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Deming Department of Medicine, Tulane Medical School, New Orleans, LA, USA., Division of Hematology and Oncology, Department of Medicine, University of Cincinnati Cancer Center, Cincinnati, OH, USA., Worldwide Health Economics and Outcomes Research US Market, Bristol Myers Squibb, Princeton, NJ, USA., US Medical Oncology, Bristol Myers Squibb, Princeton, NJ, USA., Worldwide Health Economics and Outcomes Research Markets, Bristol Myers Squibb, Uxbridge, UK., Analysis Group, Inc., Los Angeles, CA, USA., Patient Centered Solutions, IQVIA, Bratislava, Slovakia., Patient Centered Solutions, IQVIA, Amsterdam, The Netherlands., Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA., Department of Medical Social Sciences, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA. Electronic address: ., Interdisciplinary Department of Medicine, University of Bari "A. Moro", Bari, Italy. Electronic address: .