EDITOR’S UPDATE: The U.S. Food and Drug Administration approved the cancer drug Vitrakvi (previously known as larotrectinib). Vitrakvi is indicated for the treatment of adult and pediatric patients with metastatic or unresectable solid tumors that have a NTRK gene fusion without a known acquired resistance mutation, and have no satisfactory alternative treatments options or whose cancer has progressed following treatment. Read more about this landmark decision.
Connor Pearcy, 5, was born with a tumor below his knee. A teenage boy developed a cancerous thyroid tumor in his neck. Connor and the teenager have very different tumors, but they are both on the same drug. How is that possible?
A new pediatric cancer trial at Seattle Children’s is testing a drug that targets a specific set of genetic alterations associated with soft tissue tumors in different parts of the body. Connor and the other patients in the trial have tumors that harbor one of the characteristic genetic changes the drug is designed to exploit.
Dr. Katie Albert, pediatric oncologist, and Dr. Doug Hawkins, associate division chief of Hematology and Oncology at Seattle Children’s, are overseeing the trial, which is making precision medicine possible for young cancer patients.
“It’s not easy having a child born with a tumor,” Amy Pearcy, Connor’s mom, said. “I appreciate that Dr. Hawkins never gave up looking for something new to offer, and so far it seems like we have found it.”
Born with a tumor
Connor was born with a six-centimeter tumor below his right knee. He was taken to Seattle Children’s where doctors puzzled over an unclear diagnosis.
A biopsy showed the spindle cell tumor had characteristics of myofibromatosis, a rare benign tumor, and infantile fibrosarcoma, a rare cancerous tumor. The tumor didn’t fit perfectly into either condition, but doctors tried chemotherapy used for other spindle cell tumors.
“Doctors started chemotherapy when Connor was 7 weeks old and that went on for a year,” Pearcy said. “The chemotherapy didn’t have much effect on the size of the tumor as we had hoped because it only shrunk a little bit.”
Doctors stopped chemotherapy to see what would happen. The tumor began to grow again. Doctors performed surgery to remove as much of the tumor as possible, but surgical solutions were risky because a blood vessel ran straight through the tumor. Unfortunately, the tumor grew back shortly after surgery.
Long shot test leads to astonishing improvement
After chemotherapy and surgery failed to stop the tumor’s growth, the family worried they might have run out of options. Hawkins kept thinking about other approaches, and he suggested a test through the University of Washington Medical Center that would look for genetic markers in the tumor that could be targeted by newer drugs. While it was a long shot, it was worth a try after other treatment had been ineffective.
“Dr. Hawkins came in excited after he got the results,” Pearcy said. “The test came back with a positive result for a genetic marker that could be targeted.”
Hawkins began treating Connor in a clinical trial testing a new drug from Loxo Oncology called LOXO101 that targets a specific genetic pathway in the tumor. After two months, his tumor had shrunk by an astonishing 78%, and a scan after four months of treatment showed no tumor at all.
“He takes the drug twice a day with a piece of cheese,” Pearcy said. “This is an amazing milestone for us after a lot of difficult experiences when treatment wasn’t stopping the tumor.”
Targeting cancer’s genetic pathway
The drug works by targeting a class of proteins known as NTRK that can cause certain types of cancers in the brain, thyroid, breast, lung, salivary glands and connective tissues.
“A strand of DNA in a cell breaks and pairs with a NTRK gene, causing a hybrid or combined gene to turn on when it’s not supposed to be active,” Hawkins said. “The result is a cancer.”
The cancer has this unique genetic characteristic, so researchers at LOXO Oncology developed a treatment that targets only activated NTRK and the tumor itself. This is in contrast to common cancer treatment like chemotherapy and radiation, which have more widespread effects on the body.
“Radiation and standard chemotherapy drugs are effective cancer treatments, but they are non-specific,” Albert said. “In addition to targeting cancer cells, these treatments can also damage hair cells, skin cells and other normal tissues in the body. This results in substantial short- and long-term side effects.”
Doctors at Seattle Children’s are working across specialties to determine what other tumors could be targeted by this drug, which has shown no major side effects thus far.
“We’re encouraging pathologists to incorporate molecular testing in certain cases because we’re recognizing that it can change diagnosis and treatment course,” said Dr. Erin Rudzinski, a pathologist at Seattle Children’s who assesses cancer biopsies to determine diagnoses. “These tests can help us make a diagnosis more individualized to the patient.”
Rudzinski is working with Albert and Hawkins to identify more patients whose tumors have unsuspected NTRK changes.
Kindergarten and cancer treatment
Connor started kindergarten, and he has two little sisters that also keep his parents busy. Even though the tumor has impacted his childhood, he stays active — he recently attended basketball camp and loves to swim.
The constant medical appointments and tests have taken their toll on Connor and the family over the years, but they remain hopeful this drug could allow Connor to live a healthy life, unencumbered by the tumor.
“We are thankful for everyone we’ve worked with at Seattle Children’s,” Pearcy said. “I’m sure it took a lot of work to get this study going, and our family appreciates the effort because this medicine gives us renewed hope.”
- Clinicaltrials.gov: Oral TRK Inhibitor LOXO-101 for Treatment of Advanced Pediatric Solid or Primary Central Nervous System Tumors (SCOUT)
- Dr. Katie Albert, Seattle Children’s
- Dr. Doug Hawkins, Seattle Children’s
- Dr. Erin Rudzinski, Seattle Children’s
- Seattle Children’s Cancer and Blood Disorders Center