A first-of-its-kind drug targeting a fused gene found in many types of cancer was effective in 93 percent of pediatric patients tested, researchers at UT Southwestern’s Simmons Cancer Center announced.
Most cancer drugs are targeted to specific organs or locations in the body. Larotrectinib is the first cancer drug to receive FDA breakthrough therapy designation for patients with a specific fusion of two genes in the cancer cell, no matter what cancer type. The research appears in The Lancet Oncology.
“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. What’s unique about the drug is it is very selective; it only blocks TRKreceptors,” said lead author Dr. Ted Laetsch, Assistant Professor of Pediatrics and with the Harold C. Simmons Comprehensive Cancer Center.
Larotrectinib, targets TRK fusions, which can occur in many types of cancer. While the TRK fusions occur in only a small percentage of common adult cancers, they occur frequently in some rare pediatric cancers, such as infantile fibrosarcoma, cellular congenital mesoblastic nephroma, and papillary thyroid cancer, said Dr. Laetsch, who leads the Experimental Therapeutics Program (ETP) in the Pauline Allen Gill Center for Cancer and Blood Disorders at Children’s Health in Dallas.
“Every patient with a TRK fusion-positive solid tumor treated on this study had their tumor shrink. The nearly universal response rate seen with larotrectinib is unprecedented,” Dr. Laetsch said.
Among them was 13-year-old Briana Ayala of El Paso, who aspires to a career in fashion design. In 2016, Briana was found to have a rare tumor in her abdomen wrapped around her aorta, the largest artery in the body.
Surgeons in her hometown said it would be too dangerous to operate, so her family brought Briana to Children’s Health in Dallas, where UT Southwestern Professor of Surgery Dr. Stephen Megison had to remove portions of her aorta while removing most of the tumor.
But the cancer started to grow again and no further treatments were available.
Dr. Laetsch sent her tumor for genetic testing and found that Briana’s cancer had the TRK fusion, meaning the new drug might help.
Briana enrolled in the phase 1 clinical trial of larotrectinib and began taking the drug twice a day. Within weeks her pain and the swelling in her abdomen diminished, and scans showed her tumors had shrunk significantly.
Nearly two years later, Briana is back in school and playing with her dog, Goofy, and the family’s seven parakeets. She’s also been able to pick up her sketch pad and her dreams of a New York City fashion career.
“These are the kind of amazing responses we’ve seen with larotrectinib,” said Dr. Laetsch, “and this is why I’m so excited about it.”
The results of the larotrectinib trial in adult patients – a 75 percent response rate – were published last month in the New England Journal of Medicine.
The TRK-fusion mutation can be present in many types of cancers, including lung, colon, thyroid, and breast cancer, as well as certain pediatric tumors. TRK, short for tropomyosin receptor kinase, is a gene that plays a key role in brain and nervous system development and has a limited role in nervous system functions such as regulating pain in later life.
Larotrectinib belongs to a class of molecules known as kinase inhibitors, which work by cutting back on the enzymatic activity of a key cellular reaction. The selectivity of the drug means it does not cause the severe side effects associated with many traditional cancer treatments, and none of the patients with TRK fusions had to quit the study because of a drug-induced side effect.
Equally important, the response was long-lasting for most patients. “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,” said Dr. Laetsch, who investigates the use of tumor molecular profiling to guide therapy in UT Southwestern’s Pediatric Hematology and Oncology Division.
A next step in the research is a clinical trial involving a similar drug for those patients who developed resistance. Dr. Laetsch will be the national leader for that clinical trial in children.
The Latest on: Larotrectinib
via Google News
The Latest on: Larotrectinib
- Europe Gives the Go-Ahead on Cancer Treatment Pillon October 5, 2019 at 7:53 am
Well, we’re getting there. In September, the European Medicines Agency approved Bayer’s Vitrakvi®, otherwise known as the equally catchy name: larotrectinib. It was also approved in November 2018 by ...
- High Response Rate, Durability Maintained With Larotrectinib in TRK Fusion Canceron September 30, 2019 at 7:08 am
An updated analysis confirmed the potential of the targeted therapy larotrectinib (Vitrakvi, Bayer) for use in children and adults with tropomyosin receptor kinase (TRK) fusion cancer, according to ...
- Positive Larotrectinib Data for TRK Fusion Cancer Presented at ESMOon September 29, 2019 at 8:17 am
At the ESMO Congress 2019, Ulrik Lassen, MD, PhD, professor of oncology at the University of Copenhagen, discussed the newly-released clinical data highlighting new overall survival and ...
- Bayer Announces Updated Analysis for Vitrakvi® (...on September 28, 2019 at 12:20 am
WHIPPANY, N.J., Sept. 28, 2019 /PRNewswire/ -- Updated clinical data for Vitrakvi ® (larotrectinib) in adult and pediatric patients with TRK fusion cancer demonstrated an overall response rate (ORR) ...
- EU OK for First 'Histology-Independent' Cancer Drugon July 26, 2019 at 5:41 am
The product is larotrectinib (Vitrakvi, Bayer), which targets a specific gene mutation, the neurotrophic tyrosine receptor kinase (NTRK) gene fusion. Larotrectinib is indicated for the treatment of ...
- Larotrectinib: Targeting DNA in cancer therapyon December 3, 2018 at 7:23 am
CHLA's Leo Mascarenhas, MD, MS, saw promise in larotrectinib when he helped design the clinical trial testing its safety and efficacy, but nobody could have foreseen just how dramatic the results ...
- NTRK Drug Wins Approval for All Solid Tumorson November 27, 2018 at 6:24 am
WASHINGTON – The FDA approved the oral agent larotrectinib (Vitrakvi) on Monday for treating metastatic or unresectable solid cancers of any type that harbor a neurotrophic receptor tyrosine kinase ...
- FDA Approves Vitrakvi® (larotrectinib), the First Ever TRK Inhibitor, for Patients with Advanced Solid Tumors Harboring an NTRK Gene Fusion(1,2)on November 26, 2018 at 5:47 pm
I have seen firsthand how treatment with larotrectinib, which is designed specifically for this oncogenic driver, can deliver clinically meaningful responses in patients with TRK fusion cancer, ...
- FDA approves an oncology drug that targets a key genetic driver of cancer, rather than a specific type of tumoron November 26, 2018 at 2:39 pm
The U.S. Food and Drug Administration today granted accelerated approval to Vitrakvi (larotrectinib), a treatment for adult and pediatric patients whose cancers have a specific genetic feature ...
via Bing News