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New Drug Shows Promise Against Many Kinds Of Cancers

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Contributed byMaulik P. Purohit MD MPHJul 10, 2017

Some form of genetic change is inevitable in cells. These small genetic changes may drive the cell to grow out of control and produce a tumor mass. TRK (tropomyosin receptor kinase) gene mutation is one of the genetic changes found in many cancers. The product of this gene abnormality produces tropomyosin receptor kinase fusion protein that helps in cancer cell growth. It may be described as an ignition switch for cancer cell growth and division. An abnormality in TRK gene is found in about 0.5 to 1% of many common cancers, and in over 90% of some rare cancers including salivary gland cancer, infantile fibrosarcoma, and juvenile breast cancer. Researchers even say that it is hard to find cancer where TRK gene abnormality has not been reported.

Treatment against genetic changes or products resulting from genetic changes has been long since tried with varying successes. Such treatments are called targeted therapy since they target a specific change. Recently, a drug called “Larotrectinib” has been tried that specifically inhibits the tropomyosin receptor kinase fusion protein (or TRK gene abnormality). Although previous experimental drugs that blocks TRK along with other protein are in use, Larotrectinib is the first drug that is known to selectively blocks TRK.

Researchers analyzed data from 3 ongoing phases I and II clinical trials. All the 55 patients enrolled in the study had locally-advanced or metastatic cancers of the colon, salivary glands, lung, pancreas, thyroid, gastrointestinal tract, other sarcomas and skin cancers like melanoma, totaling 17 types of cancer. All these cancers had the TRK gene abnormality. Age group of the enrolled patients ranged from 12 to 43 years.

The result of the study was promising. More than 75% of the patients responded well to Larotrectinib. It was interesting to note that three pediatric patients with sarcoma, previously not amenable to surgery, went on to have a potentially curable surgery after Larotrectinib reduced the size of cancer. One year into treatment, almost 80% of the patient responded to treatment and remained progression-free. It is worth mentioning that no patients had to stop or discontinue treatment, because of any side effects. The study is ongoing and more results of this “new treatment” is still awaited.

Larotrectinib had gained the designation of a breakthrough therapy, by the US-based Food and Drug Administration (FDA), in 2016, for pediatric and adult cancer. This study finding is further proof of its effectiveness. The lead author of the study, Dr. Hyman said that “this dataset, subject to independent central radiology review, will be submitted to FDA for Larotrectinib’s regulatory approval. If approved, Larotrectinib could become the first therapy of any kind to be developed and approved simultaneously in adults and children, and the first targeted therapy to be indicated for a molecular definition of cancer that spans all traditionally-defined types of tumors.

He also added that “these findings embody the original promise of precision oncology: treating a patient based on the type of mutation, regardless of where the cancer originated. We believe that the dramatic response of tumors with TRK fusions to Larotrectinib supports widespread genetic testing in patients with advanced cancer, to see if they have this abnormality.

Written By Krish Tangella MD, FCAP

 

References:

New Drug Shows Durable Efficacy Across Diverse Pediatric and Adult Cancers [Internet]. ASCO. 2017 [cited 2017 Jun 29]. Available from: https://www.asco.org/about-asco/press-center/news-releases/new-drug-shows-durable-efficacy-across-diverse-pediatric-and

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Maulik P. Purohit MD MPH

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