TRK Inhibitor Proves Beneficial in Primary CNS Tumors

0

The TRK inhibitor larotrectinib (Vitrakvi) showed activity in patients with TRK fusion-positive primary central nervous system (CNS) tumors, according to an analysis of two trials.

Among 33 patients with primary CNS tumors, the median overall survival (OS) had not been reached over 16.5 months of follow-up, and the 1-year OS rate was 85%, reported Sébastien Perreault, MD, of CHU Sainte-Justine University Hospital in Montreal.

The median progression-free survival (PFS) was 18.3 months, and the 1-year PFS rate was 56%.

Larotrectinib is active in this “population with a high unmet need for tolerable targeted therapeutic options,” Perreault said during a presentation at the virtual American Society of Clinical Oncology (ASCO) annual meeting.

Among the patients with CNS gliomas, the objective response rate (ORR) — the primary endpoint — was 26% (95% CI 9-51%) in patients with high-grade gliomas and 38% (95% CI 9-76%) in those with low-grade gliomas.

Even though the ORRs were not particularly high, the time to response was just 1.9 months, and these were all heavily pretreated patients, noted ASCO discussant Jaishri Blakeley, MD, of Johns Hopkins University in Baltimore.

However, controlling the tumors came with a high rate of treatment-related adverse events (AEs). While most AEs were grade 1 or 2, about 39% of patients experienced grade 3/4 events. There were no grade 5 events, nor any deaths due to treatment-emergent AEs. None of the patients discontinued treatment due to AEs. Two patients required dose reductions, and 11 patients had to skip doses.

Larotrectinib is highly effective against TRK fusion-positive cancer, Perreault noted. NTRK gene fusions encode chimeric TRK proteins, which are constitutively active and act as oncogenic drivers in a wide variety of adult and pediatric solid tumors. The fusions are found in about 1% of all solid tumors and in about 2% of adult primary brain tumors, he said.

Perreault and colleagues analyzed data from two trials: NAVIGATE, which enrolled nine patients ages 12 and older with advanced TRK fusion-positive solid tumors; and SCOUT, which included 24 patients under the age of 21 with locally advanced or metastatic solid tumors or CNS tumors.

Of the 33 patients included in the analysis, median age was 8.9 years, and 52% were male. Twenty-seven patients had gliomas, of which 58% were high grade and 24% were low grade. NTRK2 fusions were the most prevalent, found in 73% of patients.

Perreault said the success of the two trials called for genetic testing for NTRK gene fusions in patients of all ages with primary CNS tumors.

Although it may be akin to looking for a needle in a haystack, “studies show truly remarkable response rates when the appropriate therapy is applied to the right variant,” said Blakeley.

“These studies prove that there are a subset of central nervous system tumors that are driven on specific targeted pathways,” she noted. “These targetable tumors are ultra-rare; they do require that the care team has done the dedicated molecular testing to show the variant is detectable and targetable, but it is well worth the effort because the long-term response rate and clinical benefit can be just remarkable.”

“On the shadow side of that,” she added, “is these drugs require continuous use and have toxicity profiles that can significantly affect quality of life.”

  • Ed Susman is a freelance medical writer based in Fort Pierce, Florida, USA.

Disclosures

The study was supported by Bayer Healthcare.

Perreault disclosed relationships with AstraZeneca, Bayer, Eisai, and Novartis.

Blakeley disclosed relationships with Astellas Pharma.

Stay connected with us on social media platform for instant update click here to join our  Twitter, & Facebook

We are now on Telegram. Click here to join our channel (@TechiUpdate) and stay updated with the latest Technology headlines.

For all the latest Health News Click Here 

 For the latest news and updates, follow us on Google News

Read original article here

Denial of responsibility! TechiLive.in is an automatic aggregator around the global media. All the content are available free on Internet. We have just arranged it in one platform for educational purpose only. In each content, the hyperlink to the primary source is specified. All trademarks belong to their rightful owners, all materials to their authors. If you are the owner of the content and do not want us to publish your materials on our website, please contact us by email – admin@techilive.in. The content will be deleted within 24 hours.
Leave a comment