In the phase 3 JAVELIN Renal 101 trial (NCT02684006), first-line treatment with avelumab + axitinib resulted in significantly longer progression-free survival (PFS) and a higher objective response rate (ORR) vs sunitinib in patients with advanced renal cell carcinoma (aRCC). We report the final analysis, including the primary analysis of overall survival (OS).
Patients with untreated aRCC (any prognostic risk score) were enrolled. Primary endpoints were OS and PFS in the programmed death ligand 1-positive (PD-L1+) population. ORR, duration of response (DOR), safety, and patient-reported outcomes (PROs) were also assessed.
Minimum follow-up was 68 months in all patients. Median OS (95% CI) with avelumab + axitinib vs sunitinib, respectively, was 43.2 (36.5-51.7) vs 36.2 (29.8-44.2) months in the PD-L1+ population (hazard ratio [HR], 0.86 [95% CI, 0.701-1.057]; P=0.0755) and 44.8 (39.7-51.1) vs 38.9 (31.4-45.2) months in the overall population (HR, 0.88 [95% CI, 0.749-1.039]; P=0.0669). Investigator-assessed PFS remained prolonged with avelumab + axitinib vs sunitinib (5-year event-free rate [95% CI] in the overall population, 12.0% [8.9%-15.6%] vs 4.4% [2.5%-7.3%]). ORR (95% CI) in the overall population was 59.7% (55.0%-64.3%) with avelumab + axitinib vs 32.0% (27.7%-36.5%) with sunitinib; DOR (95% CI) was ≥5 years in 16.4% (12.0%-21.4%) vs 9.2% (4.6%-15.7%), respectively. Rates of grade ≥3 treatment-related adverse events were 66.8% vs 61.5%, respectively. PROs were similar between arms.
JAVELIN Renal 101 provides the longest follow-up to date for immune checkpoint inhibitor + tyrosine kinase inhibitor combination treatment from a phase 3 trial in aRCC. OS analyses favored avelumab + axitinib vs sunitinib but did not reach statistical significance; subsequent treatment may have impacted results. Avelumab + axitinib provided long-term efficacy benefits vs sunitinib, including prolonged PFS, a nearly doubled ORR, and more durable responses, with a manageable long-term safety profile.
Annals of oncology : official journal of the European Society for Medical Oncology. 2024 Dec 18 [Epub ahead of print]
T K Choueiri, K Penkov, H Uemura, M T Campbell, S Pal, C Kollmannsberger, J L Lee, B Venugopal, A J M van den Eertwegh, S Negrier, H Gurney, L Albiges, R Berger, J B A G Haanen, V Oyervides Juárez, B I Rini, J Larkin, F Nolè, M Schmidinger, M B Atkins, Y Tomita, B Ellers-Lenz, J Hoffman, R Sandner, J Wang, A di Pietro, R J Motzer
The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: ., Private Medical Institution, Euromedservice, St. Petersburg, Russian Federation., Department of Urology, Kindai University Faculty of Medicine, Osakasayama, Japan., Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., City of Hope, Duarte, CA, USA., BC Cancer - Vancouver Centre, Vancouver, BC, Canada., Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea., Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, UK., Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands., University of Lyon, Centre Léon Bérard, Lyon, France., Department of Clinical Medicine, Macquarie University, Sydney, NSW, Australia., Institut Gustave Roussy, Villejuif, France., The Chaim Sheba Medical Center, Ramat Gan, Israel., Netherlands Cancer Institute, Amsterdam, the Netherlands., Hospital Universitario Dr. Jose Eleuterio Gonzalez, Centro Universitario Contra el Cancer, Monterrey, Mexico., Vanderbilt-Ingram Cancer Center, Nashville, TN, USA., Royal Marsden NHS Foundation Trust, London, UK., Istituto Europeo di Oncologia, Milan, Italy., Medical University of Vienna, Vienna, Austria., Georgetown University Medical Center, Washington, DC, USA., Department of Urology and Department of Molecular Oncology, Niigata University Graduate School of Medicine, Niigata, Japan., Merck Healthcare KGaA, Darmstadt, Germany., EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA., Pfizer, Collegeville, PA, USA., Pfizer, Cambridge, MA, USA., Pfizer srl, Milan, Italy., Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: .