Real-World Study Demonstrates Safety and Efficacy of Avelumab/Axitinib in Advanced RCC

First-line avelumab (Bavencio) in combination with axitinib (Inlyta) was effective and safe in a real-world population of patients with advanced renal cell carcinoma (RCC) and delivered results consistent with those previously reported in clinical trials, according to findings from the primary analysis of the AVION study.1

At the data cutoff of July 5, 2024, 104 patients with advanced RCC enrolled across Belgium, Germany, Greece, and Russia who received the combination in routine clinical practice achieved a median overall survival (OS) that was not reached (NR) 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%).

In an interview with OncLive®, Axel Merseburger, MD, PhD, professor and chair of the Department of Urology at University Hospital Schleswig-Holstein in Lübeck, Germany, discussed the rationale for evaluating avelumab plus axitinib in a real-world setting, the design of the study, and how the results compared with prior clinical trial data.2 He also highlighted efficacy, safety, and discontinuation findings, as well as the potential role of this regimen for selected patients with advanced RCC in the context of evolving treatment guidelines.

OncLive: What was the rationale for conducting this study of avelumab plus axitinib in a real-world setting for patients with advanced RCC?

Merseburger: The rationale and the idea was we have the approval in a lot of countries for [avelumab and axitinib] for treating advanced and metastatic RCC. We wanted to have a look [at whether] these trial data, which were published and shown at several conferences, [would] hold [up] in real-world data, in countries like Russia, Greece, [and] Germany, [which] were the countries included in the AVION trial.

What key aspects of the study design should be highlighted, including patient characteristics and how treatment was administered?

This was an all-[comer] study [in] metastatic RCC, and initially we planned to recruit 250 patients. Due to [political issues] with some of the centers in Russia and recruitment difficulties, we [ended enrollment] after 104 fully recruited patients. This is the first report now published out of the AVION trial and these real-world data.

How did these real-world findings compare with prior clinical trial data in terms of efficacy?

One of the end points [of this real-world analysis] is to compare to the [phase 3] JAVELIN Renal 101 trial [NCT02684006.], which [led] to [the] approval of the combination in a lot of countries. [With the real-world study], we basically echoed the results we saw in [the] clinical trial. In real-world data collection, [findings were[consistent with the previously published data with regard to OS and progression-free survival [PFS].

The median OS has not been reached yet, but we could display, the 12-month OS, and after 12 months, more than 82% of the patients were still alive. When you look at the details in the patient demographics and characterization, there were some patients with poor prognosis [and] intermediate prognosis, so this reflected a real-world scenario where patients were treated in the AVION trial. The median PFS was also very consistent at 11.3 months and comparable to the pivotal trial that led to approval of the [combination].

The overall response rate was 46% [with a good] disease control rate, and the toxicity was pretty mild, especially when looking at [grade 3 or higher adverse effects]. [It was] within a single digit and again, also showing the good toxicity profile of this combination.

What factors typically influence treatment discontinuation, and how do safety outcomes with this regimen translate into clinical practice?

It really depends on what toxicity was displayed. We know some toxicity comes more from the [avelumab], and then some more from the TKI—for instance, diarrhea was TKI-derived. This is something where you can dose reduce, and you see it pretty [quickly] because of the very short half-life of axitinib. We tend to stop the axitinib first and then see, if it's not getting better, we also had to stop the avelumab.

References

1. Merseburger A, Baklanova O, Garlonta V, et al. Real-world effectiveness and safety of first-line (1L) avelumab + axitinib in patients with advanced renal cell carcinoma (aRCC): primary analysis of the AVION study. J Clin Oncol. 2025;43(suppl 5):474. doi:10.1200/JCO.2025.43.5_suppl.474
2. Motzer RJ, Penkov K, Uemura H, et al. Avelumab + axitinib vs sunitinib in patients (pts) with advanced renal cell carcinoma (aRCC): final overall survival (OS) analysis from the JAVELIN Renal 101 phase 3 trial. J Clin Oncol. 2024;42(suppl 16):4508. doi:10.1200/JCO.2024.42.16_suppl.4508