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Targeted immunotherapy for advanced RCC

Choueiri TK et al. Lancet Oncol. 2018 Mar 9. doi: 10.1016/S1470-2045(18)30107-4.

Key clinical point: The targeted-immune combination of axitinib and avelumab had manageable toxicity and encouraging preliminary efficacy as a front-line treatment of advanced renal cell carcinoma (RCC).

Major finding: Out of 55 patients enrolled, 26 (53%) had a response, including 3 (6%) who had complete responses.

Study details: A dose-expansion and dose-finding phase 1b study including 55 patients with advanced clear-cell RCC.

Disclosures: Funding for the study came from Pfizer and Merck. Study authors declared interests related to several companies, including Pfizer, Merck, Bristol-Myers Squibb, Novartis, Roche/Genentech.

Source: Choueiri TK et al. Lancet Oncol. 2018 Mar 9. doi: 10.1016/S1470-2045(18)30107-4

Read the full article.

Citation:

Choueiri TK et al. Lancet Oncol. 2018 Mar 9. doi: 10.1016/S1470-2045(18)30107-4.

Commentary:

Commentary by Viktor Grünwald, MD, PhD

The antitumor activity of axitinib and avelumab in this study indicate the potential clinical benefit of targeted-immune combinations for advanced renal cell carcinoma (RCC).

Further studies are warranted to explore whether a first-line targeted-immune combination might overcome the standard of sequential targeted and immune therapies.

The current absence of long-term safety data for the combination approach is limiting in terms of making definitive conclusions about the toxicity of axitinib and avelumab as a first line combination therapy for advanced clear-cell RCC, Dr. Grünwald wrote.

Even so, axitinib has a “low” incidence of hepatic toxicity, making it a “preferable” agent to evaluate in targeted-immune combination trials such as JAVELIN Renal 100.

Objective responses in JAVELIN Renal 100 were seen in 32 out of 55 patients (58%), of which 3 patients (6%) were complete responses, according to reported data.

Similar findings previously reported for the immune-immune combination of ipilimumab and nivolumab versus sunitinib. In that study, patients receiving the immune-immune combination had an overall response rate of 42% and complete response rate of 9%, while the group patients receiving sunitinib had overall and complete response rates of 27% and 1%, respectively.

With the dawn of immune-immune and targeted-immune combinations, for the first time in a decade, major progress towards improving the median overall survival and possibly delivering cure to some of our patients with metastatic renal-cell carcinoma seems to have been made.

Viktor Grünwald, MD, PhD, is with the department of hematology, haemostasis, oncology, and stem cell transplantation at Hannover Medical School, Germany. These comments are based on an editorial accompanying the report (Lancet Oncol. 2018 Mar 9. doi: 10.1016/S1470-2045[18]30126-8). Dr. Grünwald disclosed ties to Bristol-Myers Squibb, Merck Sharp and Dohme, Ipsen, Novartis, Roche, AstraZeneca, Pfizer, Cerulean, Eisai, and EUSA Pharma.

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