Expert Point of View: Bernard Escudier, MD

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A phase III trial is warranted. I would want positive phase III data before I give cabozantinib to poor- and intermediate-risk patients.
— Bernard Escudier, MD

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Formal discussant of this trial, Bernard Escudier, MD, Chairman of the Renal Cancer Unit at Institut Gustave Roussy, Villejuif, France, said: “The main question is whether this study will change practice.” He is not so sure it will and would like more data.

Dr. Escudier told listeners that the European guidelines for renal cell carcinoma dramatically changed from 2014 to 2016, mainly in second- and third-line options. “What is striking is that first-line recommended treatment has not changed since 2009, despite several clinical trials,” he noted.

“Cabozantinib [Cabometyx] has broader targets than sunitinib. Both AXL and MET are overexpressed after sunitinib [Sutent] treatment, and cabozantinib targets both of these in addition to being a potent VEGFR inhibitor, so there is a good rationale to study cabozantinib vs sunitinib in first-line therapy,” Dr. Escudier said.

Cautious Optimism

“From this study, we learned that cabozantinib is more active than sunitinib for progression-free survival and has impressive response rates compared with suninitib. Survival is numerically improved, but we cannot say for certain that cabozantinib will improve survival. It is not clear that these data are convincing enough,” he continued. “The overall survival data should be interpreted with caution.”

“It is a major breakthrough for a [tyrosine kinase inhibitor] to beat sunitinib in the front-line setting. My personal conclusion is that cabozantinib is superior to sunitinib in poor- and intermediate-risk patients, and it will probably be active in good-risk patients. Despite that, a phase III trial is warranted. I would want positive phase III data before I give cabozantinib to poor- and intermediate-risk patients,” he said.

Dr. Escudier said that several studies presented at the 2016 European Society for Medical Oncology (ESMO) Congress and published in 2015 and 2016 might lead to changes in the ESMO 2016 guidelines. They include the current study of cabozantinib as first-line therapy in poor- and intermediate-risk renal cell carcinoma, a study of sunitinib in the adjuvant setting in high-risk patients, [see page 5 of this issue for more on this study], and a study of nivolumab (Opdivo) in renal cell carcinoma, and perhaps lenvatinib (Lenvima) plus everolimus (Afinitor, Zortress) as third-line therapy. ■

Disclosure: Dr. Escudier reported no potential conflicts of interest.

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