The US Food and Drug Administration (FDA) has approved the immunotherapy avelumab (Bavencio, Merck and Pfizer) in combination with the tyrosine kinase inhibitor axitinib (Inlyta, Pfizer) for the first-line treatment of patients with advanced renal cell carcinoma (RCC).
This is the first FDA approval of an anti–programmed cell death–ligand-1 (anti-PD-L1) therapy as part of a combination regimen for patients with advanced RCC, according to a joint statement from the companies.
However, this not the first approval of an immunotherapy-plus-axitinib combination in this setting.
The new approval is based on safety and efficacy results from the phase 3 JAVELIN Renal 101 study, which were reported in the New England Journal of Medicine earlier this year.
The investigators reported that among the 560 patients with PD-L1–positive tumors (63.2%), the median progression-free survival was 13.8 months with avelumab plus axitinib, as compared with 7.2 months with sunitinib (Sutent, CPPI CV) (hazard ratio for disease progression or death, 0.61; P < .001).
In the larger intention-to-treat (ITT) overall study population of 886 patients, the median progression-free survival was 13.8 months, as compared with 8.4 months (hazard ratio, 0.69; P < .001).
The study’s ITT population included patients regardless of PD-L1 expression across all prognostic risk groups (favorable risk, 21%; intermediate risk, 62%; poor risk, 16%).
Among the patients with PD-L1–positive tumors, the objective response rate was 55.2% with avelumab plus axitinib and 25.5% with sunitinib. The median follow-up period for overall survival was 11.6 months with avelumab plus axitinib and 10.7 months with sunitinib. In the group that received the combination therapy, 37 patients died; among those who received sunitinib, 44 patients died. However, overall survival data from the trial are not yet mature.
When interim data from the study were presented at the annual meeting of the European Society of Medical Oncology in 2018, at a press conference, investigator Robert Motzer, MD, said regarding their findings, “I don’t believe you need to test [PD-L1] to choose patients for this therapy.”
Motzer, who is from Memorial Sloan Kettering Cancer Center, New York City, added: “It may be that…the hazard ratio is a little better in the PD-L1-positive group, but I don’t think it’s required to use this medicine. I think it can be given regardless of PD-L1 status.”
The most common adverse reactions with avelumab plus axitinib (≥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% of patients who received avelumab plus axitinib. The incidence of major adverse cardiovascular events was higher with the combination than with sunitinib.
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