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Avelumab/Axitinib Approved: Advanced Renal Cell Carcinoma

Renal clear cell carcinoma.

The FDA has approved avelumab (Bavencio®, EMD Serono, Inc.) in combination with axitinib (Inlyta®, Pfizer Inc.) as first-line treatment for advanced renal cell carcinoma (RCC).

Avelumab is an anti–programmed death ligand 1 (anti–PD-L1) antibody, a type of immune checkpoint inhibitor. Axitinib, a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI), improves tumor infiltration by immune cells. It has antiangiogenic activity, meaning that it prevents tumors from growing their own blood vessels.

"As we look to continue to improve outcomes for people with advanced RCC, new treatment approaches have the potential to benefit patients," commented Robert J. Motzer, MD, Jack and Dorothy Byrne Chair in Clinical Oncology at Memorial Sloan Kettering Cancer Center in New York and principal investigator of the JAVELIN Renal 101 trial (NCT02684006), on which the approval was based. "With today's 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."

For the JAVELIN Renal 101 study, 886 patients with untreated advanced RCC were randomized to receive either 10 mg/kg of intravenous avelumab every 2 weeks plus 5 mg oral axitinib twice daily or 50 mg of oral sunitinib—the standard-of-care first-line therapy for advanced RCC—once daily for the first four weeks of a six-week cycle until radiographic progression of disease or unacceptable toxicity. The trial's co-primary end points were progression-free survival and overall survival in the subset of 560 patients with PD-L1–positive tumors. A key secondary end point was progression-free survival in the overall study population, with other secondary end points including objective response and safety.

Avelumab/axitinib increased median progression-free survival compared with sunitinib, both for patients with PD-L1–positive tumors (13.8 vs 7.2 months) and in the overall trial population (13.8 vs 8.4 months). It also demonstrated higher objective response rates in the PD-L1–positive group (55.2% vs 25.5%) and in the overall population (51.4% vs 25.7%). At a median follow-up of 19 months, data for overall survival were immature, with 27% deaths in the intent-to-treat population.

The most frequent adverse events, occurring in at least 20% of patients with RCC taking avelumab/axitinib, included diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain, and headache. Nine percent of patients experienced grade 3/4 hepatotoxicity, which resulted in a permanent discontinuation of avelumab or axitinib in 7% of patients. Seven percent of patients on avelumab/axitinib experienced major cardiac adverse events.

The recommended dose for advanced RCC is 800 mg intravenous avelumab, administered every two weeks, in combination with 5 mg oral axitinib twice daily.

For More Information

Clinicaltrials.gov (2019). A study of avelumab with axitinib versus sunitinib in advanced renal cell cancer (JAVELIN Renal 101). NLM identifier: NCT02684006.

Motzer RJ, Penkov K, Haanen J, et al (2019). Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med, 380(12):1103-1115. DOI:10.1056/NEJMoa1816047

​Image credit: KGH

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