EU Approves Bavencio + Inlyta as First-Line Therapy for Advanced Renal Cell Carcinoma Amid Intensifying Immuno-Oncology Competition

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Pfizer and Merck recently announced that the European Commission has approved the combination therapy of Bavencio (avelumab) and Inlyta (axitinib) for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). In the United States, this combination therapy was approved by the FDA in May of this year for the first-line treatment of patients with advanced RCC. Additionally, both parties submitted a supplemental application in Japan in January of this year for the use of this combination therapy in patients with unresectable or metastatic RCC.

Notably, Bavencio is the first anti-PD-L1 therapy approved by the European Union as part of a combination regimen for the treatment of advanced renal cell carcinoma (RCC). This approval was based on the interim analysis results of the Phase III JAVELIN Renal 101 study (NCT02684006). This randomized, multicenter, open-label study enrolled a total of 886 patients with previously untreated advanced RCC, regardless of tumor PD-L1 expression status. The study included patients from all International Metastatic RCC Database Consortium (IMDC) prognostic risk groups (21% favorable risk, 62% intermediate risk, and 16% poor risk) and evaluated the efficacy and safety of the Bavencio plus Inlyta combination as first-line treatment, comparing it with sunitinib, the standard-of-care agent for first-line treatment of RCC.

Analysis data with a median follow-up of 19 months showed that in patients with advanced renal cell carcinoma (RCC), regardless of PD-L1 expression status, Bavencio plus Inlyta significantly extended progression-free survival (PFS) by more than 5 months compared with sunitinib (13.3 months [95% CI: 11.1–15.3] vs. 8.0 months [95% CI: 6.7–9.8]), significantly reduced the risk of disease progression or death by 31% (hazard ratio [HR]=0.69 [95% CI: 0.574–0.825], p<0.0001), and nearly doubled the objective response rate (ORR) (52.5% [95% CI: 47.7–57.2] vs. 27.3% [95% CI: 23.2–31.6]). At the time of the interim analysis, data for the other study endpoint, overall survival (OS), were not yet mature; the OS hazard ratio for the Bavencio plus Inlyta combination versus sunitinib was 0.80 (95% CI: 0.616–1.027), and the study will continue as planned.

In terms of safety, the most common adverse reactions were diarrhea, hypertension, fatigue, nausea, dysphonia, decreased appetite, hypothyroidism, cough, headache, dyspnea, and arthralgia.

Furthermore, with this approval, the posology section of the Bavencio Summary of Product Characteristics has been updated:

The recommended dose of Bavencio as monotherapy is 800 mg, administered as a 60-minute intravenous infusion every 2 weeks; Bavencio should be continued according to the recommended schedule until disease progression or unacceptable toxicity.

For the combination regimen of Bavencio and Inlyta, the recommended dose of Bavencio is 800 mg administered as a 60-minute intravenous infusion every 2 weeks, and the dose of Inlyta is 5 mg taken orally twice daily (approximately 12 hours apart), until disease progression or unacceptable toxicity.

Intensifying Competition in First-Line Treatment for Advanced RCC

Renal cell carcinoma (RCC) is the most common type of kidney cancer, accounting for approximately 90% of all cases. It is estimated that 20–30% of patients with RCC present with advanced-stage disease at initial diagnosis. Many patients with advanced RCC do not receive subsequent therapy after first-line treatment, due to reasons such as suboptimal efficacy of the initial regimen or adverse events. The 5-year survival rate for patients with metastatic RCC is only 12%. There is a significant unmet medical need in this field for first-line therapies that can delay disease progression and have an acceptable safety profile.

In addition to Bavencio + Inlyta, two other first-line combination regimens incorporating cancer immunotherapy have been approved in the United States and the European Union: Bristol Myers Squibb’s Opdivo + Yervoy immunotherapy combination was approved in the US in April 2018 and in the EU in January 2019 for the first-line treatment of patients with advanced renal cell carcinoma (RCC) at intermediate or poor risk per the International Metastatic RCC Database Consortium (IMDC) criteria; Merck’s Keytruda + Inlyta combination therapy was approved in the US in April 2019 and in the EU in September 2019 for the first-line treatment of patients with advanced RCC at favorable, intermediate, or poor risk per the IMDC criteria.

This latest approval also signifies that competition among three combination regimens containing tumor immunotherapy for the first-line treatment of renal cell carcinoma (RCC) has fully unfolded in the US and European markets.

Bavencio, Opdivo, and Keytruda are all PD-(L)1 immunotherapies designed to harness the body’s own immune system to fight cancer by blocking the PD-1/PD-L1 signaling pathway, thereby inducing cancer cell death. These therapies have currently become important treatment options for various types of tumors. In renal cell carcinoma (RCC), PD-L1 expression may suppress the immune response against tumor cells; furthermore, RCC is a highly vascular tumor in which vascular endothelial growth factor (VEGF) plays a key role. This underpins the mechanism of action for the combination regimens of Bavencio plus Inlyta and Keytruda plus Inlyta.

It is worth noting that these two “immunotherapy + targeted therapy” combinations share the same mechanism of action, demonstrate similar efficacy in pivotal Phase III clinical trials, and exhibit consistent efficacy across subgroups stratified by IMDC risk criteria (low, intermediate, and high risk) as well as by PD-L1 expression status (PD-L1-positive and PD-L1-negative).

Reference Source:

1、European Commission Approves BAVENCIO? (avelumab) Plus Axitinib Combination for First-Line Treatment of PatientsWith Advanced Renal Cell Carcinoma

2. Competition Intensifies Among First-Line Renal Cell Carcinoma Therapies! Bavencio + Inlyta Combination Therapy Approved by the FDA