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• Immunotherapy drug plus targeted agent provided better progression-free survival and shrank tumors in more patients than standard one-drug treatment
• Side effects were similar in both treated groups

News — BOSTON - A combination of two drugs – one of them an immunotherapy agent – could become a new standard, first-line treatment for patients with metastatic kidney cancer, says an investigator from , reporting results from a phase 3 clinical trial.

Patients who received the immunotherapy drug avelumab plus axitinib, a VEGF targeted agent, had a significant advantage in progression-free survival compared with those who received sunitinib (Sutent), a VEGF targeted drug that has been a standard treatment for advanced clear cell renal cell carcinoma – the most common form of kidney cancer.

“Patients receiving the drug combination also had a higher response rate – meaning their tumors shrank – than the sunitinib-only group,” said , senior and co-corresponding author of the report on the JAVELIN Renal 101 trial in The New England Journal of Medicine and Director of the Lank Center for Genitourinary Oncology at Dana-Farber.

“This is certainly better than sunitinib -- hopefully this will lead to Food and Drug Administration approval soon,” said Choueiri, The Jerome and Nancy Kohlberg Professor of Medicine at Harvard Medical School

While progression-free survival was improved with the combination treatment, additional follow-up is needed to show whether the two-drug therapy extends overall survival compared to the standard regimen.

The trial is the first pivotal study to combine avelumab with a drug that targets the vascular endothelial growth factor receptor (VEGFR). VEGFR blockers like sunitinib and axitinib are designed to starve tumors by disrupting their blood supply. Immunotherapy drugs such as avelumab – which blocks an immune checkpoint called PD-L1 – work by activating “exhausted” immune T cells so they can more effectively attack cancer cells.

The clinical trial involved 886 patients with previously untreated, advanced renal cell carcinoma who were randomized to receive the drug combination or sunitinib alone.

The results from this study showed that the median progression-free survival (PFS) – the length of time before the cancer began to worsen – was 13.8 months in the combination group and 7.2 months in patients receiving only sunitinib. These results specifically applied to patients whose cancer cells tested positive for the PD-L1 checkpoint that is blocked by avelumab. The PFS for the overall population (PD-L1 positive or negative) was consistent – 13.8 months versus 8.4 months.

The proportion of patients whose tumors shrank was 55.2 percent with avelumab plus axitinib and 25.5 percent with sunitinib in the patients who were positive for PD-L1.

“Interestingly, the analysis showed that all subgroups – favorable, intermediate, and poor-risk patient – benefited from the combination treatment,” said Choueiri. This was the topic of an oral presentation Choueiri has just given at the 2019 Genitourinary Cancers Symposium in San Francisco. The results were simultaneously published in the New England Journal of Medicine.

Nearly all patients in both treatment groups experienced some side effects. In the combination treatment group, 38.2 percent of patients experienced immune-related adverse events, the most frequent being thyroid disorders, observed in 107 patients.

Choueiri said that for patients with advanced disease, “this is an important option.  What we’re doing in advanced kidney cancers is pushing the envelope – these treatments may not be curative, but patients are living longer, and the disease is becoming more chronic.”

The clinical trial is sponsored by Pfizer, Inc., and is part of an alliance between Pfizer and Merck KGaA.

Dr. Choueiri reports grants, personal fees and non-financial support from Pfizer, during the conduct of the study; grants and personal fees from Astra Zeneca, grants and personal fees from Bayer, grants and personal fees from BMS, grants and personal fees from Cerulean, grants and personal fees from Esai, grants and personal fees from Foundation Medicine Inc., grants and personal fees from Exelixis, grants and personal fees from Genentech, grants and personal fees from Roche, grants and personal fees from GlaxoSmithKline, grants and personal fees from Merck, grants and personal fees from Novartis, grants and personal fees from Peloton, grants and personal fees from Pfizer, grants and personal fees from Prometheus Labs, grants and personal fees from Corvus, grants and personal fees from Ipsen, grants from Tracon, personal fees from Alligent, personal fees from Up-to-Date, personal fees from NCCN, personal fees from Analysis Group, personal fees from Michael J. Hennessy (MJH) Associates, Inc. (Healthcare Communications Company and several brands such as OnClive and PER), personal fees from L-path, personal fees from Kidney Cancer Journal, personal fees from Clinical Care Options, personal fees from Platform Q, personal fees from Navinata Healthcare, personal fees from Harborside Press, personal fees from American Society of Medical Oncology, personal fees from NEJM, personal fees from Lancet Oncology, grants from Calithera, grants from Takeda, outside the submitted work

About Dana-Farber

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