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FDA Actions & Updates

The latest approvals, designations, and new indications from the U.S. Food and Drug Administration for oncology drugs.

Wednesday, May 15, 2019

Avelumab Plus Axitinib Approved For Patients With Advanced Renal Cell Carcinoma

The FDA has approved avelumab in combination with axitinib for the first-line treatment of patients with advanced renal cell carcinoma (RCC). This is the first FDA approval for an anti-PD-L1 therapy as part of a combination regimen for patients with advanced RCC.

The approval of avelumab in combination with axitinib was based on positive results from the phase III JAVELIN Renal 101 study (NCT02684006), in which the combination significantly improved median progression-free survival (PFS) compared with sunitinib by more than 5 months in the intent-to-treat (ITT) patient population (HR: 0.69 [95% CI: 0.56–0.84]; 2-sided p-value=0.0002; median PFS for avelumab in combination with axitinib: 13.8 months [95% CI: 11.1-NE]; sunitinib: 8.4 months [95% CI: 6.9-11.1]). The ITT population included patients regardless of PD-L1 expression and across IMDC (International Metastatic Renal Cell Carcinoma Database) prognostic risk groups (favorable 21%, intermediate 62% and poor 16%).

"As we look to continue to improve outcomes for people with advanced RCC, new treatment approaches have the potential to benefit patients," said Robert J. Motzer, MD, Jack and Dorothy Byrne Chair in Clinical Oncology, Memorial Sloan Kettering Cancer Center, and principal investigator for JAVELIN Renal 101. "With [this] FDA approval of avelumab in combination with axitinib, we can now offer patients with advanced RCC a first-line treatment option that combines a PD-L1 immunotherapy with a well-known VEGFR TKI to provide a significant reduction in the risk of disease progression or death and doubling of the response rate compared with sunitinib."

"A kidney cancer diagnosis is life-changing for both patients and their loved ones, and having a treatment strategy for their disease quickly becomes a priority," said Dena Battle, President, KCCure. "The approval of new treatments such as avelumab in combination with axitinib gives patients with advanced RCC much-needed options."

There is a significant unmet need for first-line treatments that delay progression and have an acceptable safety profile. Approximately 20 percent to 30 percent of patients are first diagnosed with RCC at the advanced stage, and 30 percent of patients treated for an earlier stage go on to develop metastases. About half of patients living with advanced RCC do not go on to receive additional treatment after first-line therapy.

In JAVELIN Renal 101, the objective response rate (ORR) was doubled in the ITT population with avelumab in combination with axitinib versus sunitinib (51.4% [95% CI: 46.6-56.1] vs. 25.7% [95% CI: 21.7-30.0]). With a median overall survival (OS) follow-up of 19 months, data for the trial's other primary endpoint of OS were immature, with 27 percent of deaths in the ITT population, and the trial is continuing as planned. The most common adverse reactions (≥20%) were diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain, and headache. Serious adverse reactions occurred in 35 percent of patients receiving avelumab in combination with axitinib. The incidence of major adverse cardiovascular events (MACE) was higher with avelumab in combination with axitinib versus sunitinib. Findings from the study have been published in The New England Journal of Medicine (2019;380:1103-1115).

The European Medicines Agency validated the Type II variation application for avelumab in combination with axitinib in advanced RCC in March 2019, and a supplemental application for avelumab in combination with axitinib in unresectable or metastatic RCC was submitted in Japan in January 2019.