Research for renal cancer combo drugs picks up

Drug combinations against advanced kidney cancer are the new focus in research and treatment, say many oncology experts. One combination in the news is nivolumab and ipilimumab, each an immunotherapy drug. The first approved (2016) combination for advanced kidney cancer is everolimus plus lenvatinib.

Other combinations, which include some of the aforementioned drugs, are also being tested, in a new era that medical oncologist James Hsieh is calling the Golden Era for advances against kidney cancer.

The types of treatments that are being combined use the properties of vascular endothelial growth factor (VEGF) in drugs that shut down blood supply to tumors (e.g., lenvatinib); of mTOR pathway drugs that block the regulation of cellular metabolism and proliferation (e.g., everolimus); and more recently, of PD-1/PD-L1 immunotherapies that are checkpoint proteins on T cells (e.g., pembrolizumab).

“I see a future where we can take a look at a patient’s cancer genomics, figure out what kind of treatment they will benefit from as a frontline, and then we can use a very good combination like VEGF treatment plus PD-1/PD-L1 (antibodies), and I think we should be able to achieve very durable remission for 30% or more of kidney cancer patients,” said Hsieh of Sloan-Kettering Memorial Hospital in New York for OncLive.com.

In an interview with TargetedOnc.com, Thomas E. Hutson, DO, PharmD, director of the Genitourinary Oncology Program at the Texas Oncology-Charles A. Sammons Cancer Center Baylor University Medical Center, said of the Study 205 findings on lenvatinib and everolimus that “combination therapy is here to stay for kidney cancer.” That trial demonstrated that lenvatinib plus everolimus reduced the risk of progression or death by 63% compared with everolimus alone.

Another example is the combination of immunotherapies nivolumab (brand name Opdivo) and ipilimumab (Yervoy), which is in early-stage clinical trials. The (London) Independent newspaper noted: “The results from CheckMate-016 (an early Phase 1 trial) are encouraging, and warrant further study, as they show with nearly two years of follow-up, 40.4% of patients in each nivolumab plus ipilimumab combination arm responded to the regimen, with the majority of responses occurring early and within the first few months of treatment,” quoting Hans Hammers, MD, a kidney cancer specialist from the University of Texas Southwestern Medical Center in Dallas.

“There remains a significant unmet need for treatment options that offer ongoing responses and increase survival for patients with renal cell carcinoma,” Hammer said.

Baylor’s Hutson noted that at the 2016 European Society of Medical Oncology Congress there was news of a variety of combinations that will be employed. “With combination therapy, there is the toxicity concern that we will need to make judgments about,” he said. “People often bring up cost of care when we bring up combination therapy. That is something that we, as a society, are going to have to address.”

He noted that another combination trial is in a Phase 3 study. It will be a three-arm study comparing lenvatinib (Lenvima) plus everolimus (Afinitor), versus lenvatinib and pembroizumab (Keytruda), versus a single drug, sunitinib (Sutent).

Another drug, cabozantinib (Cabometyx), is in a Phase 1b combination trial with immunotherapies through work with manufacturer Exelixis’ collaborators at the National Cancer Institute, according to the company. The trial will explore cabozantinib in combination with nivolumab alone, or in combination with nivolumab plus ipilimumab, in patients with genitourinary tumors, including renal cell carcinoma.

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