In a phase III JAVELIN Renal 101 study conducted in patients with previously untreated advanced renal cell cancer (RCC), final overall survival (OS) analyses favoured avelumab plus axitinib versus sunitinib alone, but differences did not reach prespecified significance boundaries. This is the longest follow-up to date for immune checkpoint inhibitor (ICI) plus tyrosine kinase inhibitor (TKI) combination treatment in a phase III study in advanced RCC.
Progression-free survival (PFS) and objective response rate (ORR) per investigator assessment were substantially improved with avelumab plus axitinib, consistent with prior analyses. The findings were reported by Dr Toni K. Choueiri of the Dana-Farber Cancer Institute in Boston, MA, US, Dr. Robert J. Motzer of the Memorial Sloan Kettering Cancer Center in New York, NY, US and colleagues on 17 December 2024 in the Annals of Oncology.
In previous analyses from the phase III JAVELIN Renal 101 study, avelumab plus axitinib showed significantly longer PFS versus sunitinib in the PD-L1-positive population (primary endpoint) and overall population and nearly doubled the ORR; however, OS data (primary endpoint) were immature. The study investigators reported in the latest manuscript, published in the Annals of Oncology, the results from the final analysis of JAVELIN Renal 101, including the primary analysis of OS.
Patients with previously untreated advanced RCC (any prognostic risk score) were enrolled in the study. The primary endpoints were OS and PFS in the PD-L1-positive population. ORR, duration of response (DoR), safety, and patient-reported outcomes (PROs) were also assessed. The minimum follow-up was 68 months in all patients.
The median OS with avelumab plus axitinib versus sunitinib was 43.2 months (95% confidence interval [CI] 36.5-51.7 months) versus 36.2 months (95% CI 29.8-44.2 months) in the PD-L1-positve population (hazard ratio [HR] 0.86, 95% CI 0.701-1.057; p = 0.0755) and 44.8 months (95% CI 39.7-51.1 months) versus 38.9 months (95% CI 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 plus axitinib versus sunitinib with 5-year event-free rate in the overall population of 12.0% (95% CI 8.9% to 15.6%) versus 4.4% (95% CI 2.5% to 7.3%).
ORR in the overall population was 59.7% (95% CI 55.0% to 64.3%) with avelumab plus axitinib versus 32.0% (95% CI 27.7% to 36.5%) with sunitinib; DoR was ≥5 years in 16.4% (95% CI 12.0% to 21.4%) versus 9.2% (95% CI 4.6% to 15.7%), respectively.
Long-term follow-up confirmed the safety profile of avelumab plus axitinib, and no new safety signals were identified. Rates of grade ≥3 treatment-related adverse events were 66.8% versus 61.5%, respectively. PROs during treatment were similar between arms, suggesting that adding avelumab to TKI treatment had no adverse impact on health-related quality-of-life. As PROs were measured every 6 weeks, which corresponded to ‘off-treatment’ weeks in the sunitinib arm, results may not be representative of average symptom burden with sunitinib.
The authors concluded that in JAVELIN Renal 101, OS analyses favoured avelumab plus axitinib versus sunitinib, but did not reach statistical significance; subsequent treatment may have impacted results. Avelumab plus axitinib provided long-term efficacy benefits versus sunitinib, including prolonged PFS, a nearly doubled ORR, and more durable responses, with a manageable long-term safety profile.
This work was supported by Pfizer and was previously conducted under an alliance between Merck and Pfizer. Analyses were supported by Merck and Pfizer.
Reference
Choueiri TK, Penkov K, Uemura H, et al. Avelumab + axitinib versus sunitinib as first-line treatment for patients with advanced renal cell carcinoma: final analysis of the phase III JAVELIN Renal 101 trial. Annals of Oncology; Published online 17 December 2024. DOI: https://doi.org/10.1016/j.annonc.2024.12.008