Ezra E.W. Cohen, MD

Formal discussant of the -LIBRETTO-001 trial, Ezra E.W. Cohen, MD, Associate Director for Translational Science and Leader of the Solid Tumor Therapeutics Research Program at the Moores Cancer Center at UC San Diego Health, was encouraged by this trial and said that detection of genetic alterations is key.

“We know that selpercatinib is effective in lung and thyroid cancers; in this global, multicenter, basket study using the RET inhibitor in other cancers, we saw fairly high activity. The objective response rate was 47% across all tumors enrolled. Responses appear to be durable, and three-quarters of responses are ongoing at 13 months,” he said.

RET alterations occur across a variety of cancers but in a small percentage of patients with these cancers. “RET was first recognized in medullary thyroid cancers, and now we recognize that RET fusions can occur in multiple cancers. They are mainly fusions, and the fusion partners are considerable. The activity of selpercatinib appeared to be irrespective of fusion partner,” Dr. Cohen noted.

Proactive Approaches to Molecular Profiling

“RET alterations are detectable with DNA-based approaches. RNA-based approaches are becoming available and require higher tumor volume. Cell-free circulating tumor DNA is emerging as a testing modality, but it may not select all fusions,” stated Dr. Cohen.

“There are new rules,” he continued. “The molecular profiling of patients must become universally available. It is no longer a question of if but how we do molecular profiling. We need health policy and guidelines for testing. Selective targeting yields fewer patients but greater efficacy with a targeted treatment. We need to develop proactive approaches. The toxicities of each targeted therapy are unique, and educating providers is essential.” 

DISCLOSURE: Dr. Cohen has served as a consultant or advisor to Bayer, -BioNTech, Eisai, Gilead, Merck, MSD, and Regeneron.