Yohann Loriot, MD, PhD

FORMAL DISCUSSANT of the RANGE trial at the ESMO 2017 Congress, Yohann Loriot, MD, PhD, of the Institut Gustave Roussy and University of Paris-Saclay, Villejuif, Paris, said that although the study met its primary endpoint, he was not sure the absolute improvement in progression-free survival is clinically relevant in view of the lack of improvement in quality of life. He agreed that overall survival data are needed. 

It makes sense to study angiogenesis, he continued. “Angiogenesis is one of the hallmarks of bladder cancer. But based on all the key trials so far, only the combination with bevacizumab (Avastin) holds promise. Toxicity is a key concern in this group of frail patients with comorbidities,” he said. 

“The strengths of the RANGE study are that it met its primary endpoint, reported the best objective response rates in second-line treatment of unselected patients, had manageable safety, and improved progression-free survival. Maybe this is the best angiogenesis inhibitor ever studied in bladder cancer,” he continued. 

Nevertheless, he added, “limitations of the study are the small progression-free survival benefit, lack of survival data, no improvement in quality of life, and no biomarkers to identify which patients will respond.” 

Possible Role in Treatment 

DR. LORIOT suggested that pembrolizumab (Keytruda) may be a preferred option in this setting. “In KEYNOTE-045, pembrolizumab improved quality of life over chemotherapy. Pembrolizumab may be the preferred option over other treatments, but some patients have disease progression very quickly on pembrolizumab.” 

He concluded: “Perhaps ramucirumab will find a role in daily practice. In some patients with a short response to first-line therapy and no visceral metastasis, maybe the combination of ramucirumab/docetaxel could be given in the second-line setting.” ■ 

DISCLOSURE: Dr. Loriot has served as an advisor to Astellas, Clovis, Roche, Ipsen, Janssen, MSD, Sanofi, and AstraZeneca.