Rozlytrek Offers ‘New Frontier’ for Treating Brain Metastases in NTRK Fusion-Positive Cancers

Treatment with a tyrosine kinase inhibitor (TKI) called Rozlytrek (entrecinib) demonstrated meaningful responses in patients with NTRK fusion-positive solid tumors who had brain metastases and may be an option for addressing this unmet need.

The findings — published in Clinical Cancer Research — suggest the drug could help address an unmet need for patients whose cancer has spread to their central nervous system.

“So obviously, this is a rare disease, because the frequency of this interaction is very low,” said study author Dr. Christian Rolfo, professor of Hematology and Medical Oncology at the Icahn School of Medicine at Mount Sinai and Associate Director for Clinical Research in the Center for Thoracic Oncology at The Tisch Cancer Institute in New York, during an interview with CURE®.

NTRK is a gene fusion — which occurs when a piece of the chromosome containing the NTRK gene splits off and joins with an unrelated gene on a different chromosome — that when present, indicates that someone may be more likely to respond to specific cancer therapies like Rozlytrek. The fusion occurs in around .3% of all solid tumors, according to an article published in Nature.

The recent study that reported on Rozlytrek in brain metastases used data from three clinical trials to examine the drug’s effectiveness after one year. The ability of the drug to cross the blood-brain barrier was not seen in the initial trials.

The main goals were overall response rate (ORR; which shows the percentage of patients whose cancer responds to treatment) and duration of response (DoR; length of time a tumor continues to respond without growing or spreading).

“We have an overall response rate of around 60%, but the most important thing that you will see is that brain metastases were also very well treated with these compounds. And the results that we have are confirming — around 57% — that this drug is penetrating the brain very effectively; we actually have some complete responses in the brain,” Rolfo said.

The researchers also assessed progression-free survival (PFS; length of time until disease progresses) and intracranial safety/efficacy in patients who received one or more dose of Rozlytrek.

After the data cutoff on Aug. 31, 2020, the majority of the patients (121 adults with 14 tumor types) had a complete or partial response (61.2%). Median follow-up was 25.8 months and median DoR was 20 months. In 11 patients who had measurable central nervous system metastases, the intracranial ORR was 63.6%, and median intracranial DoR was 22.1 months.

The side effects experienced were similar to previous studies, with most treatment-related events being mild or moderate and manageable with dose modification. There was a small percentage of treatment-related side effect discontinuation (8.3%).

“I think it’s a very good opportunity to encourage the doctors and the community to test these patients, because this is a rare fusion that needs to be searched (for),” Rolfo said. “But when you have this, there are multiple opportunities to be treated.”

He also added that he encourages patients to ask their doctors for genetic testing in a broad manner.

“So we now have a new frontier working in this population, first of all, to try to get an answer for patients who are progressing to the treatment or having resistance to the treatment,” Rolfo said. “And for that, it’s important that we also find a molecular profiling mechanism of resistance that we can target as well… and obviously it’s really important that we continue our research in how we can detect these patients.”

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