At the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, the broad-spectrum anticancer agent Larotrectinib (LOXO-101) presented preliminary findings that patients with cancer carrying a tropomyosin receptor kinase (TRK) kinase (TRK) gene fusion in cancer patients with an objective remission rate of 78% with Larotrectinib!
What is Larotrectinib? Why does it deliver such high remission rates? Does it work for thyroid cancer?
How does Larotrectinib work against cancer?
Larotrectinib is a broad-spectrum anti-cancer drug that specifically targets patients who have a TRK gene fusion. It is a major breakthrough in precision medicine in recent years by targeting the oncogene directly at the source of tumor formation.
TRK is a receptor that normally binds to a ligand, and a TRK fusion mutation is a fusion of a member of the NTRK (neurotrophin receptor tyrosine kinase) gene family, the gene that produces TRK, with another unrelated gene, so that TRK no longer needs to bind to a ligand to promote cell growth, especially in tumor cells. It is strongly associated with the development, metastasis, and progression of many tumors, including thyroid cancer.
The incidence of NTRK1 gene fusions is not consistent across populations (0-10.9%); the frequency of NTRK1 gene fusions is low in Chinese patients with thyroid tumors.
Larotrectinib selectively inhibits the tumor-promoting activity of TRK protein to achieve anticancer effects.
Larotrectinib fights cancer, efficiently and safely
In February 2018, the final results of a clinical trial of Larotrectinib were published, confirming its effect on TRK gene fusion cancers.
A total of 55 patients with TRK gene fusion cancers were enrolled in the study, including 5 patients with thyroid cancer. All patients were treated with Larotrectinib.
The results showed an overall efficiency of 75%, with all 5 patients with thyroid cancer having a tumor size reduction of more than 30% and 1 tumor disappearing completely.
The median time to effect of larotrectinib was 1.8 months; after a median follow-up of 9.9 months, more than half of the patients had no disease progression.
In addition to its efficacy, it has a high safety profile. The vast majority of treatment-related adverse reactions were mild to moderate, with fewer serious adverse reactions and no potentially life-threatening ones. The most common were anemia, liver function side effects, weight gain, and neutropenia. No patients in the trial discontinued the drug because of side effects, and only 5 patients decreased their dose because they could not tolerate the side effects.
We can see that Larotrectinib is highly effective and safe in treating TRK gene fusion cancers.
In March 2017, the FDA granted orphan drug (rare disease drug) status to Larotrectinib for TRK gene fusion solid tumors, and in March 2018, it was placed on the priority review pathway for marketing. It is likely that in the near future, Larotrectinib will be available for patients.