This post was originally published on February 22, 2018. It was updated on Nov. 27, 2018, to reflect the approval of Vitrakvi (larotrectinib). 

There is promising news for solid tumor patients whose cancers are caused by a rare chromosomal abnormality. On Nov. 26, 2018, the U.S. Food and Drug Administration (FDA) approved the drug Vitrakvi (larotrectinib) for treatment of children and adults with tumors that have this genetic marker. Vitrakvi, developed by LOXO Oncology, is the first targeted, oral, tumor-agnostic therapy. In simpler terms, it is a cancer drug that works well across many types of solid tumors—but only on tumors caused by a specific genetic abnormality.

Vitrakvi vs NTRK fusion tumors

The rare tumor-causing genetic abnormality that Vitrakvi was designed to inhibit is known as a TRK fusion. TRK is a family of signaling proteins that help with normal cell communication. These proteins are encoded by NTRK genes, which can become abnormally fused to other genes. These fusions lead to faulty signals that cause cancer in many sites throughout the body.

The scientists who developed Vitrakvi were going after this one specific genetic malfunction—and nothing else—to turn off or inhibit its signaling pathway. Cancer drugs have traditionally been designed based on where the cancer is located. But Vitrakvi enables us to treat patients based on what kind of mutation is causing the cancer. And with such a simple, narrow function, the drug is believed to carry a lower risk of side effects.

Multi-center trial results of Vitrakvi 

The FDA approval is based on findings from a preliminary study that appeared in the New England Journal of Medicine in February 2018. The study found that Vitrakvi demonstrated “marked and durable antitumor activity in TRK fusion-positive cancers regardless of patient age or tumor type.”

The Phase 1/2 study of the drug, coordinated through Memorial Sloan Kettering Cancer Center, followed tumor cases from more than 20 cancer centers, including patients at my institution, St. Jude Children’s Research Hospital (LOXO-TRK). We have seen truly remarkable responses—both here and in the other centers:

  • About 80% of patients responded to larotrectinib.
  • 55% of all patients are still progression-free at one year.

As the drug trial’s institutional investigator for St. Jude, I must say this response rate is unprecedented. This type of tumor is rare, but when it occurs, this drug works. It doesn’t matter where the tumor is located or what kind of NTRK fusion gene triggered it.

Prior research on inhibiting NTRK fusion genes

The science behind this treatment breakthrough parallels my colleagues’ discoveries announced in 2014, after the St. Jude-Washington University Pediatric Cancer Genome Project  identified new genetic mutations that drive tumor development, including NTRK fusion genes.

At the time, Suzanne Baker, PhD, director of our Brain Tumor Research Division, accurately predicted the importance of NTRK fusions genes in future drug development: “We want to see if these tumors might be selectively sensitive to therapies that target the pathways that are disrupted as a result of these fusion genes.”

Implications for childhood cancer patients

Although few of our patients would benefit from larotrectinib, because it does treat such a rare type of tumor, it is still a remarkable study. Dr. David Hyman at Memorial Sloan Kettering, the clinical trial’s senior author, believes this drug’s dramatic response “supports widespread genetic testing in patients with advanced cancer to see if they have this abnormality.”

The clinical challenge for each patient will be in deciding at what point in the diagnostic and treatment protocol testing should take place.

Read the FDA statement on larotrectinib: FDA approves an oncology drug that targets a key genetic driver of cancer, rather than a specific type of tumor.

Read the preliminary clinical trial results: Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med Feb 2018.