Avelumab + axitinib vs sunitinib as first-line treatment for patients with advanced renal cell carcinoma: final analysis of the phase 3 JAVELIN Renal 101 trial
Mené sur 886 patients atteints d'un carcinome à cellules rénales de stade avancé (durée de suivi : au moins 68 mois), cet essai randomisé de phase III évalue l'efficacité, du point de vue de la survie globale et de la survie sans progression, d'un traitement de première ligne combinant avélumab et axitinib
Résumé en anglais
Background: 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 and methods: 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.
Results: 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.
Conclusions: 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.
