Two years ago, 13-year old Briana Ayala, an aspiring fashion designer, faced a life-changing dilemma. Doctors found a rare tumor wrapped around her aorta, the largest artery in the body. Although they were initially able to remove most of the tumor, the cancer soon began growing again.
That’s when Briana’s doctor enrolled her into a trial for larotrectinib, an experimental cancer drug. According to scientists, it’s a first-of-a-kind drug targeting one type of gene mishap found in various cancers. Briana’s cancer shrank drastically in a matter of weeks, and she’s not the only one. Based on a small set of data including other children, doctors now say the experimental drug shrank cancer tumors in 93% of patients with rare childhood cancers.
“From my personal experience, I can tell that this is going to be the favored treatment upfront for these patients who have unoperable or resistant cancers,” Ramamoorthy Nagasubramanian, a member of the study team, told OncLive.
Usually, cancer drugs are developed for specific organs or parts of the body. On the other hand, larotrectinib takes aim at one specific kind of error in one particular gene; they target a gene called TRK and its receptor, which plays a role in nerve development.
“In some cancers, a part of the TRK gene has become attached to another gene, which is called a fusion. When this occurs, it leads to the TRK gene being turned on when it’s not supposed to be and that causes the cells to grow uncontrollably,” explains study lead Ted Laetsch, a professor specializing in pediatric cancer at the University of Texas.
While this type of fusion is uncommon in adult cancers, it’s quite frequent in rare childhood cancers of soft tissue, kidney, and a thyroid. That means that the drug can work on any part of the body if the root cause of cancer was TRK fusion.
Laetsch and colleagues say they marveled at how effective the treatment was. “Every patient with a [tumor from TRK fusion] treated on this study had their tumor shrink. The nearly universal response rate seen with larotrectinib is unprecedented.”
Nagasubramanian expressed the same in an interview with OncLive. “Traditionally, those children received chemotherapy and then would undergo surgery if they responded to chemotherapy. Chemotherapy is genotoxic and has both short- and long-term side effects. Whereas, with larotrectinib, we can achieve better results—the response rate to chemotherapy is not even close to 93%.”
More and more benefits
What’s more is that the drug kept working for patients over a long period of time.
“For some of the targeted drugs in the past, many patients responded initially, but then resistance developed quickly. To date, the response to this drug seems to be durable in most patients,” Laetsch said.
Larotrectinib doesn’t have severe side effects either, since the drug is so selective. In fact, none of the patients with TRK fusion had to quit the study because of side effects from the drug.
This time, the trial’s objective was to confirm the drug’s safety in a relatively small number of patients. The team has now embarked onto the next stage, where they examine particulars like if the new treatment works well enough, which types of cancer the treatment works for, and more about side effects and how to manage them in a bigger group of patients. When these are established, they will be working towards full FDA approval.