On 14 May 2019, the FDA approved the combination of avelumab (Bavencio®, Merck KGaA/Pfizer) plus axitinib (Inlyta®, Pfizer) for the first-line treatment of advanced renal cell carcinoma (RCC) patients.

JAVELIN Renal 101

The FDA approval was based on the randomised, multicentre, open-label JAVELIN Renal 101 trial (NCT02684006) comparing the combination of avelumab plus axitinib vs sunitinib 1:1 in 886 untreated advanced RCC patients regardless of tumour PD-L1 expression. The primary efficacy endpoints included the progression-free survival (PFS) by blinded independent central review (RECIST 1.1) and overall survival (OS) in PD-L1 positive patients. The secondary endpoints were the PFS and OS in the overall study population. Study treatments were provided until radiographic progression or unacceptable toxicity.

The JAVELIN Renal 101 showed a significant improvement in PFS favouring patients with PD-L1-positive tumours treated with the combination avelumab plus axitinib and when compared to sunitinib (HR=0.61; 95% CI, 0.48-0.79; P=0.0001). Moreover, at interim analysis, a statistically significant improvement in PFS for the overall study population was demonstrated (HR=0.69; 95% CI, 0.56-0.84; P=0.0002). The median PFS in the overall study population was 13.8 months treated with avelumab plus axitinib vs 8.4 months for patients treated with sunitinib. At a median follow-up for OS of 19 months, 27% of deaths occurred in the intent-to-treat population. The OS data were not yet mature at the time of analysis.

Safety

Common adverse reactions in ≥20% of RCC patients treated with avelumab plus axitinib included diarrhoea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnoea, abdominal pain, and headache. Nine per cent of patients experienced Grade 3 and 4 hepatotoxicities resulting in permanent discontinuation of avelumab or axitinib in 7% of patients. Finally, major cardiac adverse events occurred in 7% of patients who received the combination of PD-L1 antibody plus VEGFR tyrosine kinase inhibitor.

Full prescribing information Bavencio®.