The European Commission ( EC ) has approved Bavencio ( Avelumab ) in combination with Axitinib ( Inlyta ) for the first-line treatment of adult patients with advanced renal cell carcinoma ( RCC ).
The approval was based on positive interim results from the phase III JAVELIN Renal 101 study, which demonstrated that Avelumab in combination with Axitinib significantly lowered risk of disease progression or death by 31% ( hazard ratio, HR: 0.69 [ 95% CI: 0.574–0.825; p less than 0.0001 ] ) and nearly doubled objective response rate ( ORR; 52.5% [ 95% CI: 47.7-57.2 ] vs. 27.3% [ 95% CI: 23.2-31.6 ] ) compared with Sunitinib ( Sutent ) in patients with advanced renal cell carcinoma regardless of PD-L1 status.
The study included patients across International Metastatic Renal Cell Carcinoma Database Consortium ( IMDC ) prognostic risk groups.
Improvement in progression-free survival ( PFS ) was observed across pre-specified subgroups in patients receiving the treatment combination.
In 2018, an estimated 136,500 new cases of kidney cancer were diagnosed in Europe, and approximately 54,700 people died from the disease.
Many patients living with advanced renal cell carcinoma do not go on to receive additional treatment after first-line therapy for reasons that may include poor performance status or adverse events from their initial treatment.
The five-year survival rate for patients with advanced renal cell carcinoma is approximately 12%.
The EC’s decision follows the U.S. Food and Drug Administration ( FDA ) approval of Bavencio in combination with Axitinib for the first-line treatment of patients with advanced renal cell carcinoma in May 2019.
Additionally, with this approval, the posology section of the Summary of Product Characteristics for Bavencio has been updated.
The recommended dose of Bavencio as monotherapy is 800 mg administered intravenously over 60 minutes every 2 weeks.
Administration of Bavencio should continue according to the recommended schedule until disease progression or unacceptable toxicity.
The recommended dose of Bavencio in combination with Axitinib is 800 mg administered intravenously over 60 minutes every 2 weeks and Axitinib 5 mg orally taken twice daily ( 12 hours apart ) with or without food until disease progression or unacceptable toxicity.
This approval was based on interim data from JAVELIN Renal 101, a randomized, multicenter, open-label study of Avelumab in combination with Axitinib in 886 patients with untreated advanced or metastatic renal cell carcinoma with a clear cell component.
The study included patients across risk groups ( IMDC: 21% favorable, 62% intermediate and 16% poor; Memorial Sloan Kettering Cancer Center [ MSKCC ]: 22% favorable, 65% intermediate and 11% poor ).
The primary efficacy endpoints were progression-free survival ( PFS ) as assessed by a Blinded Independent Central Review ( BICR ) using RECIST v1.1 and overall survival ( OS ) in the first-line treatment of patients with advanced renal cell carcinoma who have PD-L1-positive tumors ( PD L1 expression level greater than or equal to 1% ).
Progression-free survival based on BICR assessment per RECIST v1.1 and overall survival irrespective of PD L1 expression, objective response rate ( ORR ), time to response ( TTR ), duration of response ( DoR ) and safety are included as secondary endpoints.
The study is continuing for overall survival.
In the analysis, Avelumab in combination with Axitinib significantly improved median progression-free survival compared with Sunitinib by more than five months in patients irrespective of PD-L1 expression ( 13.3 months [ 95% CI: 11.1–15.3 ] vs. 8.0 months [ 95% CI: 6.7–9.8 ] ).
With a median follow-up for overall survival of 19 months, data for the trial’s other endpoint of OS were immature, with 27% of deaths, and the trial is continuing as planned.
The hazard ratio for OS in patients treated with Avelumab in combination with Axitinib compared with Sunitinib was 0.80 ( 95% CI: 0.616, 1.027 ) at the interim analysis.
The most common adverse reactions were diarrhea ( 62.8% ), hypertension ( 49.3% ), fatigue ( 42.9% ), nausea ( 33.5% ), dysphonia ( 32.7% ), decreased appetite ( 26.0% ), hypothyroidism ( 25.2% ), cough ( 23.7% ), headache ( 21.3% ), dyspnea ( 20.9% ), and arthralgia ( 20.9% ). ( Xagena )
Source: Merck KGaA & Pfizer, 2019