Follow-Up Data on Bayer’s Larotrectinib Hints at Potentially Curative Impact

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It’s been a month since cancer drug developers presented their latest research at the American Society of Clinical Oncology (ASCO) annual meeting, and the highlights are still reverberating across the industry.

Updates on Bayer’s Vitrakvi (larotrectinib) were presented across several sessions, including one regarding the efficacy and safety of the oral medicine in pediatric patients with tropomyosin receptor kinase (TRK) fusion-positive cancer.

BioSpace connected with Theodore Laetsch, M.D., lead investigator of the pediatric SCOUT trial, to gain more insight into the drug, the study and how patients' lives are being affected.

Laetsch is a pediatric oncologist who serves as director of both the developmental therapeutics program (DVL) and the very rare malignant tumors program (VRMTP) at the Children’s Hospital of Philadelphia. He is also an associate professor of pediatrics at the University of Pennsylvania.

He shared with BioSpace that he originally began working in medicine because his mom was a pediatrician. When Laetsch was in high school, she helped to connect him with a pediatric oncologist from Arizona who simultaneously did laboratory research and cared for patients. “I really loved that mix of being able to help individual patients, but also being able to try to enhance the field. I never changed my mindset.”

Mechanism of Action Against NTRK Fusions

Bayer’s larotrectinib works by blocking neurotrophic tyrosine receptor kinase (NTRK) gene fusions, which are genetic changes that occur in certain cancers. Laetsch said they believe these fusions are one of the events that can prompt the formation of cancer.

“This medicine blocks that genetic change, which turns off the signaling that drives cancers,” he said. “We've seen that it causes many cancers to shrink quickly in the setting of having one of those genetic changes, but it doesn't work in any tumors that don't have that genetic change.”

NTRK fusions happen across a range of cancer types. Laetsch explained that in some rare pediatric cancers, such as infantile fibrosarcoma and congenital mesoblastic nephroma, there can be NTRK fusion-positive tumors. “There are common pediatric cancers, like brain tumors, where NTRK fusions do occur, but rarely. Most children don’t have an NTRK fusion, but a few do. The medicine works in both of those types of tumors,” he said.

Larotrectinib is effective in both pediatric and adult patients. “In adults, the same kind of genetic changes happen in lung cancer and colon cancer. The medicine works regardless of the tumor type if there's an NTRK gene fusion present.”

Larotrectinib is Showing Curative Potential

Updates on the ongoing trial announced at ASCO include that “we’ve continued to accrue patients and also follow patients for longer, which means that we have longer follow-up data. We have more patients with a few additional diagnoses that weren't seen in the original data set that we published and presented before,” Laetsch said.

He shared the story of one of the very first patients in the trial, a girl with a large sarcoma in the back of her abdomen that was wrapped around her aorta and spread to her lungs. “She had a lot of fluid from the tumor in her abdomen,” he said.

They started the medicine, and within a couple of weeks, the fluid had resolved. Laetsch said that “the first scan showed that the tumor had shrunk dramatically. She went on to have a complete response, which meant that there was no more tumor that we could find in her body. She has now been on therapy and doing quite well for more than five years.”

He also highlighted patients with localized tumors, most of whom were suffering from infantile fibrosarcoma. Larotrectinib caused their tumors to shrink to the point that surgical removal was possible, and then they were able to stop taking the medicine altogether. “We have examples of patients that have been able to stop the medicine for several years and not have tumors reoccur. We're hopeful that for those patients this combination of medicine and surgery may be curative, and that they may not need any further therapy.”

Larotrectinib was approved by the U.S. Food and Drug Administration (FDA) in 2018 for children and adults with NTRK gene fusions in metastatic or locally advanced tumors, or in patients without other treatment options. “We’re continuing to study and gain additional information about how best to use this drug in children, and what the long-term effects of the medicine are,” Laetsch said.

For some patients, this medication could take the place of chemotherapy. “We're now conducting a study through the Children's Health Group to evaluate the use of larotrectinib as the first therapy that patients with NTRK fusion-positive cancer receive to try to see if we can spare the need for traditional chemotherapy and its associated side effects.”

The doctor shared that for some patients, such as the girl with a sarcoma in her abdomen, the treatment can have a life-changing impact. “She had a tumor that had progressed through standard chemotherapy. There really were no other treatment options for her. This therapy was clearly life-saving,” he said. “I think there are different impacts in different patients, but certainly we've seen profound impacts on patients for whom these genetic alterations have been identified.”

The SCOUT trial will continue to follow patients, monitoring long-term side effects.

An important aspect of larotrectinib is that it only works for patients who have NTRK fusions. Laetsch emphasized the importance of testing tumors for these genetic mutations as well as others. “If you don’t test, you'll never know whether the patient may benefit. There are other medications targeting other genetic changes in tumors that are showing really promising results recently. I focus a lot of my time on suggesting that patients get genetic testing to try and understand the driver of their tumor.”