Novel, Targeted Therapies for Patients with Advanced, RET-Positive NSCLC

Patients with advanced non-small cell lung cancer (NSCLC) often respond poorly to existing treatments. Cleveland Clinic’s Vamsidhar Velcheti, MD, Associate Director for Immuno-Oncology Research, hopes to improve outcomes for these patients using molecular-targeted and immunotherapeutic treatments. He and his team have already demonstrated good clinical activity in one therapy and are currently enrolling patients in a trial of another novel agent.

Lenvatinib shows promise

Dr. Velcheti’s group presented findings from an open-label, phase 2 clinical trial of the multiple tyrosine kinase inhibitor (TKI) lenvatinib in patients with RET-positive adenocarcinoma of the lung at the European Society for Medical Oncology 2016 Congress in Copenhagen.

“RET fusions occur in 1 to 2 percent of patients with lung adenocarcinoma, and the lenvatinib inhibits RET kinase,” said Dr. Velcheti. “We hoped that this new drug would be an effective treatment for lung cancer patients with RET gene alterations.”

In this global study led by Dr. Velcheti, lenvatinib demonstrated promising clinical activity in patients with RET-positive NSCLC, with a majority of patients showing tumor shrinkage, RET fusions and disease control. Toxicities were also manageable with dose modification. More than three-quarters of patients (19 patients) showed a durable clinical response in tumor shrinkage, with nearly half maintaining a response for 23 or more weeks, for a clinical benefit rate of 48 percent.

Patients previously treated with RET therapy achieved a better response to lenvatinib than those not receiving RET inhibitors before the study. Overall response rate was 14 percent, durable clinical response was 86 percent and clinical benefit rate was 57 percent, in contrast with 17, 72 and 44 percent for patients with no prior RET-inhibitor treatment.

“We found that lenvatinib is a novel potential treatment for patients with RET-positive NSCLC,” says Dr. Velcheti.

ISO better response rates

Although lenvatinib and other, similar drugs appear to have good clinical activity in patients with RET gene alterations, the response rates are modest. Novel, highly potent and specific RET inhibitors are under active investigation in a quest for improved outcomes.

Dr. Velcheti and his team are investigating one of these novel drugs targeting RET kinase in a clinical trial currently enrolling patients at Cleveland Clinic.

“RET gene alterations are very rare in lung cancer,” says Dr. Velcheti. “It’s absolutely critical that patients participate in clinical trials to get access to the latest and potentially effective treatments.”

Photo Credit: ©Russell Lee