Avelumab Combo Improves Long-Term Efficacy Vs Sunitinib in Advanced RCC

"In conclusion, final analysis results from [the] JAVELIN Renal 101 trial showed long-term efficacy benefits, a manageable safety profile, and stable quality of life with first-line avelumab [plus] axitinib in patients with [advanced] RCC," according to the study authors.

While combining avelumab (Bavencio) with axitinib (Inlyta) did not significantly improve overall survival (OS) vs sunitinib (Sutent) among those with advanced renal cell carcinoma (RCC), the combination therapy conferred benefits in other long-term efficacy outcomes, according to results from the phase 3 JAVELIN Renal 101 trial (NCT02684006) published in Annals of Oncology.¹

With a median follow-up of 73.7 months in the avelumab combination arm and 73.6 months in the sunitinib arm, the median OS across the overall population was 44.8 months (95% CI, 39.7-51.1) and 38.9 months (95% CI, 31.4-45.2) in each respective arm (HR, 0.88; 95% CI, 0.749-1.039; P = .0669). Among patients with PD-L1–positive disease, the median OS was 43.2 months (95% CI, 36.5-51.7) vs 36.2 months (95% CI, 29.8-44.2), respectively (HR, 0.86; 95% CI, 0.701-1.057; P = .0755).

Data showed that avelumab/axitinib significantly prolonged progression-free survival (PFS) vs sunitinib across the overall population (HR, 0.66; 95% CI, 0.566-0.769) and the PD-L1–positive population (HR, 0.57; 95% CI, 0.469-0.697). Additionally, the confirmed objective response rate (ORR) was 59.7% (95% CI, 55.0%-64.3%) vs 32.0% (95% CI, 27.7%-36.5%) in the overall population (odds ratio [OR], 3.226; 95% CI, 2.406-4.279; P <.0001) and 64.8% (95% CI, 58.8%-70.5%) vs 31.4% (95% CI, 26.1%-37.1%) across the PD-L1–positive population (OR, 4.197; 95% CI, 2.863-6.021; P <.0001).

“The final OS analyses favored avelumab [plus] axitinib vs sunitinib, but differences did not reach prespecified significance boundaries. PFS and ORR per investigator assessment were substantially improved with avelumab [plus] axitinib, consistent with prior analyses,” lead study author Toni K. Choueiri, MD, Jerome and Nancy Kohlberg chair and professor of Medicine at Harvard Medical School and director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute, wrote with coauthors.¹ “In conclusion, final analysis results from [the] JAVELIN Renal 101 trial showed long-term efficacy benefits, a manageable safety profile, and stable quality of life with first-line avelumab [plus] axitinib in patients with [advanced] RCC.”

In the open-label, international phase 3 JAVELIN Renal 101 trial, 886 patients were randomly assigned to receive avelumab at 10 mg/kg intravenously every 2 weeks plus axitinib at 5 mg orally twice daily (n = 442) or sunitinib at 50 mg orally once daily (n = 444).²

The trial’s primary end points were PFS per blinded independent central review (BICR) and OS in those with PD-L1–positive disease. Secondary end points included PFS and OS in the overall population, ORR, duration of response (DOR), safety, and patient-reported outcomes (PROs).

Patients 18 years and older with histologically or cytologically confirmed advanced or metastatic RCC with clear cell components and at least 1 measurable lesion per RECIST v1.1 criteria were eligible for enrollment on the trial. Other requirements for study entry included having an ECOG performance status of 0 or 1 and adequate bone marrow, renal, and liver function.

In the avelumab/axitinib and sunitinib arms, respectively, the median time to response was 2.7 months (95% CI, 1.1-28.9) vs 2.8 months (95% CI, 1.2-37.5) in the PD-L1–positive population and 2.8 months (95% CI, 1.1-34.5) vs 2.8 months (95% CI, 1.2-65.2) in the overall population. Additionally, the median DOR in each arm was 19.3 months (95% CI, 15.1-22.3) vs 9.7 months (95% CI, 7.0-16.6) in the PD-L1–positive group and 19.4 months (95% CI, 16.4-22.3) vs 14.5 months (95% CI, 8.7-16.6) in the overall population.

More than 90% of patients in each treatment arm completed the EuroQol 5-Dimension 5-level and Functional Assessment of Cancer Therapy Kidney Cancer Symposium Index – 19 Item Version instruments across most periods in the study. Scores associated with these items were typically stable during therapy, and investigators observed no significant differences between arms.

Any-grade treatment-related adverse effects (TRAEs) occurred in 96.8% of the avelumab/axitinib arm and 96.8% of the sunitinib arm, with grade 3 or higher events reported in 66.8% and 61.5% of patients, respectively. TRAEs leading to death occurred in 6 patients of the avelumab/axitinib arm due to unspecified cause (n = 4), sudden death (n = 1), and myocarditis (n = 1); 1 patient died in the sunitinib arm due to progressive disease.

Immune-related toxicity was reported in 50.7% of patients who received avelumab/axitinib, which included grade 3 or higher instances in 14.7%. Additionally, 15.4% of patients in this arm required high doses of corticosteroids.

References

1. 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. Ann Oncol. 2024;S0923-7534(24)04987-1. doi:10.1016/j.annonc.2024.12.008. doi:10.1016/j.annonc.2024.12.008
2. A study of avelumab with axitinib versus sunitinib in advanced renal cell cancer (JAVELIN Renal 101). ClinicalTrials.gov. Updated October 29, 2024. Accessed February 11, 2025. https://tinyurl.com/mrx7afwa