Real-world data supports first-line use of avelumab plus axitinib/axitinib in advanced renal cell carcinoma

First-line avelumab plus axitinib/axitinib is effective and safe in a real-world patient population with advanced renal cell carcinoma (RCC), according to preliminary analysis of the AVION study, which was presented at the 2025 Cancer Symposium. At the data cutoff date of July 2024, among patients with advanced renal cell carcinoma (n=104) enrolled in the trial and receiving combination therapy in routine clinical practice, median overall survival (OS) (NR) was not reached, with a 6-month OS rate of 89.1% (95% CI, 81.2%-93.8%) and a 12-month OS rate of 82.7% (95% CI, 73.5%-88.9%).

Overall,AVION's results demonstrate the efficacy, safety, good tolerability and stable health-related quality of life[HRQOL] of avelumab [plus] acitinib in a heterogeneous real-world population.

Previously, the phase 3 JAVELIN Renal 101 trial (NCT02684006) showed that first-line avelumab combined with axitinib resulted in longer progression-free survival (PFS) and higher objective response rate (ORR) compared with sunitinib, and had an acceptable long-term safety profile in patients with advanced renal cell carcinoma. The final analysis of JAVELIN Renal 101 showed that in the overall population, with at least 68 months of follow-up, the investigator-assessed median PFS was 13.9 months (95% CI, 11. 1-16.6) compared with 8.5 months (95% CI, 8.2-9.7) in the sunitinib group (HR, 0.66; 95% CI, 0.566-0.769; P ≤ 0.0001). 2The ORRs of these two groups were 59.7% and 32.0% respectively (OR, 3.226; 95%CI: 2.406-4.279; P<0.0001).

In addition, the final OS analysis results of the overall population favored the combination treatment group, although the OS difference between the two groups was not statistically significant (HR, 0.88; 95% CI, 0.749-1.039; P=0.0669). The median OS of the combination was 44.8 months (95% CI, 39.7-51.1) and that of sunitinib was 38.9 months (95% CI, 31.4-45.2). JAVELINThe findings from Renal 101 support the 2019 U.S. Food and Drug Administration’s approval of avelumab in combination with axitinib for the first-line treatment of patients with advanced renal cell carcinoma. In 2019, the European Commission also approved combination therapy for this indication.

Despite these data and approvals, AVION researchers noted that real-world data on the use of the combination in clinical practice is limited. The primary endpoint was OS rate at 12 months from the date of first treatment after informed consent. Secondary endpoints include 24-month OS rate, OS duration, PFS, ORR, duration of response (DOR), disease control rate (DCR), safety and HRQOL.

Among patients with IMDC good, intermediate, and low-risk disease, the 12-month OS rates were 92.6% (95%CI, 73.5%-98.1%), 74.1% (95%CI, 58.0%-84.8%), and 82.5% (95%CI-46.1%-95.3%), respectively. Among patients with clear cell, sarcomatoid, and other histologies, these corresponding rates were 83.1% (95% CI, 73.5%-89.4%), 100% (95% CI, 100%-100%), and 66.7% (95% CI-19.5%-90.4%), respectively. The 12-month overall survival rate for patients who underwent nephrectomy (n = 69) was 86.7% (95% CI, 76.0%-92.8%), compared with 73.4% (95% CI, 53.6%-85.8%) for patients who did not undergo nephrectomy (n = 35).

In the overall population, median progression-free survival was 11.3 months (95%CI, 8.1 - not evaluable [NE]). The 6-month and 12-month progression-free survival rates were 72.5% (95%CI, 62.1%-80.5%) and 48.4% (95%CI, 37.5%-58.5%) respectively.

Among 87 patients evaluable for response, the ORR was 46.0% (95% CI, 35.2%-57.0%), including complete response (CR), partial response, stable disease, progressive disease (PD) and non-CR/non-PD rates of 4.6%, 41.4%, 31.0%, 20.7% and 2.3%, respectively. The DCR was 79.3% (95% CI, 69.3%-87.3%), and the median DOR was NR (95% CI, NE-NE).

Adverse reactions (AEs) of any grade occurred in 83.7% of patients, and 34.6% of patients experienced grade 3 or higher AEs. Adverse events led to discontinuation of avelumab or axitinib in 9.6% and 14.4% of patients, respectively. 67.3% of patients reported any treatment-related adverse event (TRAE), with 20.2% reporting grade 3 or higher TRAEs. TRAEs resulted in discontinuation of avelumab or axitinib in 6.7% and 9.6% of patients, respectively.

The most common adverse reactions were diarrhea, fatigue, hypertension, hypothyroidism, dysphonia, nausea, palmoplantar erythrodysesthesia syndrome, pruritus, weight loss, dyspnea, and hypertensive crisis. 36.5% and 14.4% of patients experienced serious adverse events and serious adverse reactions respectively. A total of 10.6% of patients received corticosteroids, immunosuppressants, or hormonal therapy to manage any grade of TRAE. Adverse events resulted in the death of 4 patients, and adverse reactions resulted in the death of 1 patient.

HRQOL was assessed using the National Comprehensive Cancer Network/Cancer Therapy Functional Assessment Renal Symptom Index-19 item version and was assessed at the patient's baseline visit and every three cycles of avelumab treatment until the end of treatment or the end of 24-month follow-up, whichever occurred first. Notably, HRQOL total and subscale scores remained mostly stable throughout the study period.

Reference materials:https://www.onclive.com/view/real-world-data-support-the-frontline-use-of-avelumab-plus-axitinib-in-advanced-rcc