Drug successfully targets cancers with tumor-specific gene mutations

February 21, 2018, Nemours Children's Health System

Pediatric and adult cancers with one of three fusion genes responds well to a new drug, larotrectinib, according to a study published today in the New England Journal of Medicine. The drug is designed to target a specific tumor gene mutation known as tropomyosin receptor kinases (TRK) that can occur in various tumor types.

"This drug represents a changing paradigm in care where we evaluate a , not only by where it exists in the body, but by the genetic mutations that are driving its growth," said Ramamoorthy Nagasubramanian, MD, an author of the study and division chief of pediatric hematology-oncology at Nemours Children's Hospital.

The study integrates findings of three phases of research, including an adult phase 1, a pediatric phase 1/2, and an adolescent/adult phase 2 study, to report on the safety and efficacy of the drug. Fifty-five patients with TRK fusion-positive cancers, detected by molecular profiling as routinely performed by each site, were enrolled across the study sites. Patients ranged in age from 4 months to 76 years old and had 17 unique cancer diagnoses, including infantile fibrosarcoma, salivary gland tumors, and thyroid cancer. Each patient received two daily doses of the drug in pill or liquid form.

Overall 75 percent of patients had their tumors respond to the treatment, with 13 percent achieving a complete and 62 percent achieving a partial response. Responding patients remained on treatment or underwent surgery with curative intent. The median time to response was 1.8 months (range 0.9 to 6.4). The median duration of response and progression-free survival had not been reached, but after one year, 71 percent of patients with a response were ongoing and 55 percent of all patients remained progression-free. The treatment was well-tolerated by . Clinically significant adverse events were uncommon and most frequently included inflammation in the liver and other organs (alanine or aspartate aminotransferase increase), fatigue, vomiting, and dizziness.

"This study's design, simultaneously testing the efficacy and safety in adults and children, represents a strong model to follow to help advance pediatric cancer research," said Nagasubramanian. "In an era where we are not only treating tumors by names, but by their genetic signature, this research allows us to move the field forward without leaving children behind, as is so often the case in pediatric research."

The study authors note that additional data reflecting longer follow-up and a larger patient population will provide further insight into the safety profile of the , as well as the durability of the response.

Explore further: Kinase inhibitor larotrectinib shows durable anti-tumor abilities

More information: Drilon, A, et al. "Efficacy of Larotrectinib in TRK Fusion-Positive Adult and Pediatric Cancers." New England Journal of Medicine (2018): 21 Feb. 2018. Web.

Related Stories

Kinase inhibitor larotrectinib shows durable anti-tumor abilities

February 21, 2018
Three simultaneous safety and efficacy studies of the drug larotrectinib reported an overall response rate of 75 percent for patients ages four months to 76 years with 17 different cancer diagnoses. All patients had tumors ...

New drug shows durable efficacy across diverse pediatric and adult cancers

June 5, 2017
Scientists may have developed the first targeted, oral, tumor-type agnostic therapy - a cancer medicine that works comparably well across many kinds of cancer, regardless of patient age. In clinical trials of adults and children ...

Rare pediatric cancer successfully treated with new targeted therapy

April 19, 2016
When a baby's life was threatened by a rare pediatric cancer that would not respond to surgery or chemotherapy, doctors at Nemours Children's Hospital rapidly, successfully shrank the tumor by 90 percent using an experimental ...

Study weighs risks and benefits of phase I trials in pediatric cancer

February 20, 2018
On average, 1 in 10 children who enroll in pediatric phase I cancer trials are improved after the trial, and 1 in 50 die from drug-related complications, according to a new systematic review and meta-analysis published this ...

Promising cancer treatment targets rare genetic flaw

June 4, 2017
An experimental cancer medicine called larotrectinib has shown promise treating a diverse range of cancers in people young and old, researchers said at a major cancer conference in the United States.

Tazemetostat shows early promise for children with certain relapsed or refractory solid tumors

October 30, 2017
Children with relapsed or refractory malignant rhabdoid tumors, epithelioid sarcomas, or poorly differentiated chordomas with a particular genetic defect tolerated treatment with the investigational drug tazemetostat well ...

Recommended for you

Researchers identify a mechanism that fuels cancer cells' growth

November 14, 2018
Scientists at the UCLA Jonsson Comprehensive Cancer Center have identified sodium glucose transporter 2, or SGLT2, as a mechanism that lung cancer cells can utilize to obtain glucose, which is key to their survival and promotes ...

A new approach to detecting cancer earlier from blood tests: study

November 14, 2018
Cancer scientists led by principal investigator Dr. Daniel De Carvalho at Princess Margaret Cancer Centre have combined "liquid biopsy", epigenetic alterations and machine learning to develop a blood test to detect and classify ...

New antibody breakthrough to lead the fight against cancer

November 14, 2018
Scientists at the University of Southampton have developed a new antibody that could hold the key to unlocking cancer's defence against the body's immune system.

Photoacoustic imaging may help doctors detect ovarian tumors earlier

November 14, 2018
Ovarian cancer claims the lives of more than 14,000 in the U.S. each year, ranking fifth among cancer deaths in women. A multidisciplinary team at Washington University in St. Louis has found an innovative way to use sound ...

Solving the mystery of NPM1 in acute myeloid leukemia

November 13, 2018
Although it has long been recognized that mutations of gene NPM1 play an important role in acute myeloid leukemia, no one has determined how the normal and the mutated forms of the protein NPM1 function.

Cognitive decline—radiation—brain tumor prevented by temporarily shutting down immune response

November 13, 2018
Treating brain tumors comes at a steep cost, especially for children. More than half of patients who endure radiation therapy for these tumors experience irreversible cognitive decline, a side-effect that has particularly ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.