Combination Immunotherapy Promising for Treatment of Renal Cell Carcinoma

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Novel targeted and immunological therapies may help improve the outlook for patients with renal cell carcinoma.
Novel targeted and immunological therapies may help improve the outlook for patients with renal cell carcinoma.

Novel targeted and immunological therapies may help improve the outlook for patients with renal cell carcinoma (RCC), according to Dr Basma Greef, of the department of oncology at the Cambridge University Hospitals NHS Foundation Trust in the United Kingdom. She and her co-author, professor Tim Eisen, published an article in the British Journal of Cancer suggesting that researchers are introducing a renaissance of immunotherapy in the treatment of RCC.1

The authors note that there is still a need for effective adjuvant treatment for resected early stage disease, as well as for the development of effective predictive and prognostic biomarkers. There is, however, reason for optimism, thanks to novel combination therapies.

“It's an exciting time in the management of renal cancer,” said Dr Greef. “Immunotherapy was in the wilderness for the treatment of renal cancer for the past decade. Renal cancer is joining the growing number of cancers with positive data for programmed death-ligand 1 (PD-L1)-directed therapy.”

Dr Greef noted that clinicians see positive data for not 1, but for several new treatments, with the real promise of durable responses: the pendulum, she claims, is shifting back to immunotherapy. Dr Greef cited evidence of prolonged overall survival for patients with metastatic RCC on treatment with nivolumab, an anti-programmed cell death protein 1 (PD-1) monoclonal antibody.

“One of the biggest challenges that we still face is preventing patients from developing metastatic disease in the first place. It is disappointing that the adjuvant trials are, to date, negative, and it will be interesting to see, over the next 5 to 10 years, whether anti-PD-1 and -PD-L1 therapy has a role to play here,” Dr Greef told Cancer Therapy Advisor.

“Another area of unmet need in renal cancer is the lack of biomarkers and genomic stratification to help guide therapeutic management. Some strides have been made, but progress is lagging behind that for other cancers.”

Thomas Schwaab, MD, PhD, associate professor of oncology and immunology at Roswell Park Cancer Institute in Buffalo, New York, agrees that a renaissance is occurring in the treatment of RCC.

According to Dr Schwaab, newer combination therapies involving immunotherapies offer promise of durable responses. “The standard immunotherapy approach to metastatic kidney cancer over the past 3 decades has been high dose interleukin-2, which may result in a complete response rate in, at best, 15% to 20% of patients, at the cost of significant toxicities.

“We are starting to understand mechanisms of action, and we are starting to investigate how to sequence different immunotherapy approaches. All of this will benefit patients with this otherwise lethal disease.”

A number of ongoing clinical trials are investigating the optimal sequencing approaches with immunotherapies for metastatic RCC; this may help improve 5-year survival rates. Five-year survival rates are poor, and complete and durable responses are far from common.

It is hoped that cancer vaccines and T-cell checkpoint inhibitors, combined with other agents, will result in a new approach to treating RCC.

Reference

  1. Greef B, Eisen T. Medical treatment of renal cancer: new horizons. Br J Cancer. 2016;115(5):505-16. doi: 10.1038/bjc.2016.230

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