TRK fusion targets multiple cancers

Patients diagnosed with a variety of advanced cancers — from thyroid to breast cancer — appear to have durable responses when treated with larotrectinib (Vitrakvi), an agent that attacks tropomyosin receptor kinase (TRK) fusion pathology, researchers reported at the virtual meeting of the American Society of Clinical Oncology.

More than 70% of patients among 116 patients from three studies achieved either a complete or objective partial response, reported Marcia Brose, MD, PhD, associate Professor of Otorhinolaryngology: Head and Neck Surgery at the Abramson Cancer Center, University of Pennsylvania, Philadelphia. She said that 11 of the patients, or 10% of the group, achieved a complete response.

Overall, about 60% of the patients also had an objective response and another 16% of patients in the studies had disease stabilization with larotrectinib. Brose said the agent was tissue agnostic — attacking the molecular cascade in cancer signaling rather that attacking cancer in a specific organ system.

What’s more impressive, she told BreakingMED, is that the responses are durable. The median duration of response for all the adults in the study was 35.2 months. Median progression-free survival was 25.8 months, she added. “We have not reached median overall survival for treatment with larotrectinib after a median of 15.8 months of therapy which means people receiving the drug are not dying,” she said. “Some patients who were treated with larotrectinib have had responses that have been durable through 51 months of therapy.”

Larotrectinib, a highly selective TRK inhibitor, is approved for the treatment of adult and pediatric cancers that harbor NTRK gene fusions. Larotrectinib 100 mg is taken twice daily until disease progresses or intolerable adverse events occur.

In the current report, Brose said patients were treated with 17 different types of cancer: thyroid cancer accounted for 22% of the cases, followed by salivary gland cancer (19%), soft tissue sarcoma (16%), lung cancer (12%), colon cancer (7%), melanoma (5%), breast cancer (5%), GIST (3%), and nine other types (2% or less each).

About 78% of the patients had received prior systemic therapy and 68% of the patients had undergone 2 or more lines of therapy.

One person in the study had to discontinue larotrectinib due to treatment-related adverse events. Most adverse events were classified as Grade 1 or 2, Brose said.

In commenting on the study, Wasif Saif, MD, deputy physician-in-chief and medical director at Northwell Health Cancer Institute, Lake Success, New York, told BreakingMED, “This is a promising attack on multiple cancers — using the genetic profile to attack a molecular process in multiple organs.

“This is exciting. We have a novel drug that can help treat many types of cancer.” He suggested that upfront testing to determine if a cancer has TRK pathology should be considered.

Brose said that TRK fusions are found in many cancers, but the level of TRK fusions vary in organ types. Twenty percent or more of sarcomas, thyroid and salivary gland tumors have TRK pathology. Brose noted that even though only 1% to 2% of lung cancers have TRK fusion pathology, there are so many lung cancers that the small percentage still translates to a lot of targets.

Brose suggested drugs such as pembrolizumab and larotrectinib that are ’tissue agnostic’ agents represent the future of cancer treatment and drug development.

She noted that among the 9% of patients who progressed despite receiving larotrectinib, some of them responded to the next generation drug that is under development.

Samuel Kailes, Contributing Writer, BreakingMED™

The study was funded by Bayer and Loxo.

Brose disclosed relevant relationships with AstraZeneca; Bayer; Blueprint Medicines; Bristol-Myers Squibb; Eisai; Genzyme; Loxo and Novartis.

Saif disclosed no relevant relationships with industry.

Cat ID: 172

Topic ID: 98,172,496,728,791,730,122,22,192,172