Avelumab/Axitinib Combo Approved in Europe for Frontline RCC

The European Commission has approved the combination of avelumab and axitinib for the frontline treatment of adult patients with advanced renal cell carcinoma.

James Larkin, MD, PhD

The European Commission (EC) has approved the combination of avelumab (Bavencio) and axitinib (Inlyta) for the frontline treatment of adult patients with advanced renal cell carcinoma (RCC), EMD Serono (Merck KGaA) and Pfizer, the codevelopers of avelumab, reported in a press release.1

The EC based its decision on findings from the phase III JAVELIN Renal 101 trial, which showed that the combination was associated with a 31% reduction in the risk of disease progression or death compared with sunitinib (Sutent) in an intent-to-treat population (ITT) of patients with treatment-naïve advanced RCC, regardless of PD-L1 expression.2

"There is a high incidence of kidney cancer in Europe, and for the most common type, renal cell carcinoma, we continue to need additional treatment options, particularly for patients with advanced disease, where outcomes are poorest," JAVELIN Renal 101 investigator James Larkin, MD, PhD, consultant medical oncologist at The Royal Marsden NHS Foundation Trust and Professor at the Institute of Cancer Research stated in the press release.

"We've seen a demonstrated efficacy benefit and safety and tolerability profile for avelumab in combination with axitinib across all prognostic risk groups in patients with advanced renal cell carcinoma, so today's approval in Europe brings an important option that can help healthcare professionals optimize treatment strategies across risk stratification," added Larkin.

The JAVELIN Renal 101 trial enrolled 886 patients with advanced or metastatic RCC, and randomized them 1:1 to receive 10 mg/kg of avelumab intravenously every 2 weeks plus 5 mg of oral axitinib twice daily in 6-week cycles or 50 mg of oral sunitinib once daily for a 4-weeks-on/2-weeks-off schedule. Patients with all MSKCC/Motzer Criteria with good- (21%), intermediate- (62%), and poor-risk disease (16%) were included.

The overall population included 560 (63.2%) PD-L1—positive patients. In the PD-L1–positive group, 270 patients received the combination and 290 patients were treated with sunitinib.

In the overall group, 442 patients were treated with the combination while 444 received sunitinib. The primary endpoints were progression-free survival (PFS) by blinded independent central review and overall survival (OS) in the PD-L1—positive group; secondary endpoints were PFS and OS in the overall population irrespective of PD-L1 status, ORR, and safety.

In the PD-L1—positive population, the median PFS was 13.8 months (95% CI, 11.1-NE) with avelumab/axitinib compared with 7.2 months (95% CI, 5.7-9.7) with sunitinib, leading to a 39% reduction in the risk of disease progression or death (HR, 0.61; 95%, 0.475-0.790; P <.0001). The ORR with the combination was 55.2% (95% CI, 49.0-61.2), which included 4 complete responses (CRs) and 51 partial responses (PRs); the ORR with sunitinib was 25.5% (95% CI, 20.6- 30.9). Twenty-seven patients in the combination arm had stable disease (SD) and 11 had progressive disease (PD).

In the overall population, the median PFS with the combination of avelumab and axitinib versus sunitinib was 13.8 months (95% CI, 11.1-NE) and 8.4 months (95% CI, 6.9-11.1), respectively (HR, 0.69; 95% CI, 0.563-0.840; 2-sided P = .0002). Moreover, the ORR with avelumab/axitinib was 51.4% (95% CI, 46.6-56.1) and 25.7% (95% CI, 21.7-30.0) with sunitinib. In the combination arm, the ORR included 3 CRs and 48 PRs; 30 patients had SD and 12 patients had PD.

In the PD-L1—positive and overall population arms, 73% and 70% of patients remained on avelumab/axitinib treatment, respectively, versus 65% and 71% of those on sunitinib. Median duration of response was not yet reached in either treatment arm in either population.

At a follow-up for median OS of 19 months, the OS endpoint remain immature with 27% of deaths in the ITT population. Pfizer, which co-develops avelumab with Merck, stated in a press release that the trial is continuing as planned.

Regarding safety, the immunotherapy/TKI regimen was found to be favorable. Fifty-one (4%) patients on the combination arm and 48 (7%) patients on the sunitinib arm experienced grade 3/4 treatment-related adverse events (TRAEs), the most common being diarrhea (5% vs 3%). All-grade TRAEs were similar between arms. Four percent of TRAEs led to avelumab/axitinib discontinuation versus 8% with sunitinib; 1 patient on avelumab/axitinib died due to TRAEs.

Grade ≥3 TRAEs were reported in 71.2% of patients in the combination arm versus 71.5% of patients in the sunitinib arm, and led to treatment discontinuations in 22.8% versus 13.4%, respectively.

In May 2019, the FDA approved the combination of avelumab and axitinib in the frontline setting for patients with advanced renal cell carcinoma, also based on the JAVELIN Renal 101 data.


  1. European Commission Approves BAVENCIO® (avelumab) Plus Axitinib Combination for First-Line Treatment of Patients With Advanced Renal Cell Carcinoma. Posted October 28, 2019. Accessed October 27, 2018. https://prn.to/2Jw39VM.
  2. Motzer RJ, Penkov K, Hannen JBAG, et al. JAVELIN Renal 101: a randomized, phase III study of avelumab + axitinib vs sunitinib as first-line treatment of advanced renal cell carcinoma (aRCC). In: Proceedings from the 2018 ESMO Congress; October 19-23, 2018; Munich, Germany. Abstract LBA6_PR.