Sylvester Study of Targeted Therapy for Lung Cancer Contributed to FDA Approval

A patient was diagnosed with non-small cell lung cancer five years ago at age 54. Shortly following the diagnosis, she received news that she carried a rare genetic rearrangement known as a RET fusion in her tumor.

RET fusions affect approximately 2% of people with non-small cell lung cancer (NSCLC) and are found in other types of malignancies as well.

Dr. Gilberto Lopes

The patient responded to standard chemotherapy at the time. “I had ‘no evidence of disease’ for three years,” she said, “and then I had a recurrence.”

On a positive note, “it was perfect timing,” she said, because she discovered a clinical trial offering targeted therapy for the first time to people with RET fusion cancers at Sylvester Comprehensive Cancer Center, part of the University of Miami Health System.

The woman enrolled in the trial of pralsetinib at Sylvester in March, and so far it’s been “a good experience.”

Leading the Sylvester site for the previous ARROW study that contributed to the FDA approval of pralsetinib in September was Gilberto de Lima Lopes Jr., M.D., M.B.A., professor of clinical medicine and co-leader of the Lung Cancer Site Disease Group at Sylvester.

“Until recently, patients with lung cancer and RET fusions, a type of molecular alteration, had no specific targeted options for treatment,” Dr. Lopes said. “Patients would usually receive chemotherapy. This trial showed that patients with RET fusions respond to pralsetinib.”

Pralsetinib (brand name Gavreto) is FDA approved for adults with metastatic RET fusion-positive NSCLC. The agency also approved the companion Oncomine Dx Target test to detect RET fusions. In a practical sense, Dr. Lopes said the approved RET fusion test is easy to use, and many platforms already test for RET fusions in common practice.

Dr. Lopes and colleagues conducted the ARROW clinical trial in 87 people with NSCLC and RET fusion gene alterations who were previously treated with standard chemotherapy. The results showed 57% of patients achieved the main outcome of overall response rate. Furthermore, among the patients who responded, 80% experienced effects lasting six months or longer.

Dr. Estelamari Rodriguez

The researchers in this multicenter trial also evaluated pralsetinib in 27 patients who had not received previous treatment. They found 70% achieved an overall response rate and 58% of people who responded had an effect lasting at least six months.

“This drug has really given hope for patients with this rare fusion mutation seen in lung cancer and thyroid cancers,” said Estelamari Rodriguez, M.D., M.P.H., associate director for community outreach-thoracic oncology at Sylvester.

“As an NCI-designated cancer center, we have access to early stage clinical trials and as such have more options for patients,” Dr. Lopes said. The next clinical trial will evaluate if chemotherapy plus immunotherapy or pralsetinib is a better option for the initial treatment of patients with advanced lung cancer and RET fusions.

“We now have the first line trial open for patients with newly diagnosed non-small cell lung cancer and RET fusions,” Dr. Lopes said, “and would be happy to answer any questions physicians or their patients have about the trial.”

The Sylvester patient plans to participate in the study for 18 months “as long as my condition is stable. Hopefully it will be,” she said.

“The results have been great. The trial is working. The nodules on my lungs have either decreased or they have disappeared.”

Tags: Dr. Estelamari Rodriguez, Dr. Gilberto Lopes, non-small cell lung cancer, RET fusion, Sylvester Comprehensive Cancer Center