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Vitrakvi Continues to Improve Survival, Safety in TRK Fusion GI Cancers

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In patients with TRK fusion GI cancers, Vitrakvi continued to show improvements regarding responses to treatment, survival and safety, research found.

In patients with TRK fusion gastrointestinal cancers, treatment with Vitrakvi (larotrectinib) continued to demonstrate long-lasting responses, longer survival and a tolerable safety profile, according to updated data from a phase 2 trial.

Data presented at the 2024 Gastrointestinal Cancers Symposium included patients from the phase 2 NAVIGATE trial.

“Larotrectinib is the first-in-class, highly selective, central nervous system-active TRK inhibitor approved for tumor-agnostic use in adult and pediatric patients with TRK fusion cancer; approval was based on tumor response and durable efficacy,” the study authors explained in their poster presentation.

There were 44 total patients in the study, in which researchers used next-generation sequencing to determine that all patients in the study had NTRK gene fusions. The median age of patients was 67 years.

Study Highlights:

  • Effective Treatment Option: Vitrakvi (larotrectinib) demonstrated long-lasting responses, improved survival and a manageable safety profile in patients with TRK fusion gastrointestinal cancers, making it a promising treatment option.
  • Tumor-Agnostic Approach: Vitrakvi, a TRK inhibitor, is approved for both adults and pediatric patients with TRK fusion GI cancer, regardless of tumor type. The approval is based on positive tumor response and durable efficacy.
  • Diverse Patient Population: The study included patients with various gastrointestinal cancers, such as colorectal, pancreatic, cholangiocarcinoma, gastric and others. Colorectal cancer patients, especially those with microsatellite instability-high, showed a promising overall response rate.
  • Safety and Tolerability: Vitrakvi demonstrated a tolerable safety profile, with most side effects being mild and manageable (grade 1 or 2). Serious side effects were reported in a small percentage of patients, but none discontinued treatment due to side effects.

According to the study, tumor types included colorectal in 26 patients, pancreatic in seven patients, cholangiocarcinoma in four patients, gastric in three patients and one each for appendiceal, duodenal, esophageal squamous cell carcinoma and hepatocarcinoma (liver cancer).

Among the patients with colorectal cancer, 15 were microsatellite instability-high (MSI-H; when microsatellite segments of DNA in tumor cells have changes/mutations), nine had undetectable MSI-H (including microsatellite stable) and two had unknown microsatellite status.

The primary endpoint (main result measured at the end of a study to see if treatment worked) was the overall response rate (ORR; percentage of patients who show a partial or complete response to treatment), according to the researchers.

At the cutoff date of July 20, 2023, the ORR for 43 patients was 28%. In particular, there were three complete responses (CR; 7%; disappearance of all signs of cancer from treatment), nine partial responses (PR; 21%; decrease in tumor size or extent of cancer in the body from treatment), 19 patients with stable disease (SD; 44%; cancer that is not increasing or decreasing in severity or extent), five with progressive disease (PD; 12%; cancer that is spreading, growing or getting worse) and seven not evaluable (16%). At 24 weeks, the disease control rate (the percentage of patients with stable disease or tumor shrinkage over a period of time) was 47% in all patients, the study determined.

The secondary endpoints of the study included duration of response (DoR; time from the start of the study until disease progression or death in patients with a PR or CR).

The other secondary endpoints were progression-free survival (PFS; time during and after treatment when a patient lives with disease but it does not worsen) and overall survival (OS; time from diagnosis or the start of treatment when a patient is still alive).

In this patient population, the median time to respond to treatment was 1.8 months. The median DoR, PFS and OS were 27.3 months, 6.1 months and 12.5 months, respectively.

Among the 25 patients with colorectal cancer, the ORR was 44%. Three patients had a CR (12%), eight had a PR (32%), 11 had SD (44%), one had PD (4%) and two were not evaluable (8%). The 24-week disease control rate was 56% in this patient population.

The median DoR, PFS, and OS for all patients with colorectal cancer were 27.3 months, 7.4 months and 29.4 months, respectively. The duration of treatment ranged from 0 to 56 or more months.

“At data cutoff, 28 (64%) (total) patients had progressed on treatment, with eight (18%) continuing treatment post-progression per investigator assessment,” the authors wrote.

At the data cutoff in July 2023, side effects occurred in ≥15% of all patients with TRK fusion GI cancers. Treatment-related side effects were “predominately grade 1 or 2,” the authors wrote, meaning the side effects were considered mild and bothersome, but not dangerous.

Serious and life-threatening side effects were reported in seven (16%) patients, in which the two most common side effects were increased alanine aminotransferase and aspartate aminotransferase, two types of enzymes commonly found on the liver that can indicate liver damage if high.

Other side effects included nausea, vomiting, anemia, diarrhea, decreased neutrophils (a type of white blood cell), decreased white blood cells, fatigue, weight decrease, dizziness and constipation. None of the patients discontinued treatment due to treatment-related side effects.

“Overall, (Vitrakvi) was well tolerated; most side effects were mild and manageable. These results demonstrate that (Vitrakvi) is a fast-acting effective treatment option for patients with TRK fusion GI cancer,” the study authors wrote. “Testing patients for NTRK gene fusions is important for early identification of those patients who can benefit from this targeted therapy.”

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