CREDIT: ANNA SHVETS, PEXELS.COM
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On the horizon — A future with minimal chemotherapy for babies with soft tissue tumorsFirst, Dr. Ted Laetsch proved that larotrectinib shrank tumors in kids who'd been treated with chemotherapy. His latest study showed larotrectinib could do the same — even without chemo.
Sometimes, Ted Laetsch, M.D. has no need to show his patients a scan to prove that treatment is working. They show up at appointments and enthusiastically declare: “It’s working. The tumor… it’s not there!”
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Unfortunately, this is not a common scenario for most children with cancer. The side effects of traditional chemotherapy make it hard for patients to feel that treatment is working, and many tumors lie deep inside the body.
Dr. Laetsch, who chairs the Children’s Oncology Group’s Rare Tumors Committee and is a pediatric oncologist at the Children’s Hospital of Philadelphia (CHOP), is dedicated to helping patients get better results with less toxic, more precise treatments. For the past 8 years, he’s been studying larotrectinib, a drug that's proven to shrink soft tissue tumors driven by a rare genetic change called a TRK fusion.
The first breakthrough came in 2018, when Dr. Laetsch and his colleagues showed that larotrectinib shrank tumors in 23 out of 24 patients with TRK-fusion tumors, most of whom had already been treated with chemotherapy.
His more recent COG-sponsored study was a little different. This study involved 18 newly-diagnosed pediatric patients with infantile fibrosarcoma, a rare tumor that nearly always has a TRK fusion. None of these children had been treated with chemotherapy yet.
This time, Dr. Laetsch wanted to see if taking larotrectinib – as a pill or a liquid twice a day at home – could actually replace the need for a group of very young infants to endure multiple rounds of chemo in the hospital or in clinic. Being able to reduce or eliminate both short- and long-term side effects of chemotherapy, while gaining treatment benefit, is a welcome outcome for patients and families.
“We found that taking larotrectinib had really profound effects on every patient. Every child’s tumor shrunk, and the side effects were much milder than from chemotherapy,” Dr. Laetsch said. “As an added bonus, these families with very young, very sick kids didn’t have to travel across the country or even leave home to receive treatment.”
This study affirms the potential of larotrectinib as a dramatically effective first-line of treatment for rare tumors with a TRK fusion. For Dr. Laetsch, these results fuel his desire to identify more genetic changes that are responsible for the growth of cancer cells, regardless of where those cancer cells occur in the body.
“Rare tumors are rare. But, together, they account for 10%-15% of all pediatric cancer. And when we can identify genetic changes that cut across different types of cancer, we have a target to aim at – and a chance of treating even more people.” Dr. Laetsch said.
Dr. Laetsch’s two larotrectinib studies focused on TRK fusions. These are found in many different types of pediatric cancers including sarcomas, thyroid cancer, an infantile form of kidney cancer, brain cancer, and leukemia. Patients with these tumors were also eligible for the COG clinical trial, and their results are now being analyzed. This demonstrates great potential for more research into targeted therapies that disarm genetic changes that are found across different cancer types.
There is also great potential for COG to fund and design other small studies that could have broad-reaching results.
“COG’s support of smaller trials is helping researchers get smarter about how to design trials. We’ve learned that we don’t need a large trial to find a small difference. We can use a small trial to make a big difference,” said Dr. Laetsch. “In this last trial, every single patient benefitted. That’s not very common. When that’s the case, it becomes obvious very quickly that we are on to something truly different.”
Dr. Laetsch, who chairs the Children’s Oncology Group’s Rare Tumors Committee and is a pediatric oncologist at the Children’s Hospital of Philadelphia (CHOP), is dedicated to helping patients get better results with less toxic, more precise treatments. For the past 8 years, he’s been studying larotrectinib, a drug that's proven to shrink soft tissue tumors driven by a rare genetic change called a TRK fusion.
The first breakthrough came in 2018, when Dr. Laetsch and his colleagues showed that larotrectinib shrank tumors in 23 out of 24 patients with TRK-fusion tumors, most of whom had already been treated with chemotherapy.
His more recent COG-sponsored study was a little different. This study involved 18 newly-diagnosed pediatric patients with infantile fibrosarcoma, a rare tumor that nearly always has a TRK fusion. None of these children had been treated with chemotherapy yet.
This time, Dr. Laetsch wanted to see if taking larotrectinib – as a pill or a liquid twice a day at home – could actually replace the need for a group of very young infants to endure multiple rounds of chemo in the hospital or in clinic. Being able to reduce or eliminate both short- and long-term side effects of chemotherapy, while gaining treatment benefit, is a welcome outcome for patients and families.
“We found that taking larotrectinib had really profound effects on every patient. Every child’s tumor shrunk, and the side effects were much milder than from chemotherapy,” Dr. Laetsch said. “As an added bonus, these families with very young, very sick kids didn’t have to travel across the country or even leave home to receive treatment.”
This study affirms the potential of larotrectinib as a dramatically effective first-line of treatment for rare tumors with a TRK fusion. For Dr. Laetsch, these results fuel his desire to identify more genetic changes that are responsible for the growth of cancer cells, regardless of where those cancer cells occur in the body.
“Rare tumors are rare. But, together, they account for 10%-15% of all pediatric cancer. And when we can identify genetic changes that cut across different types of cancer, we have a target to aim at – and a chance of treating even more people.” Dr. Laetsch said.
Dr. Laetsch’s two larotrectinib studies focused on TRK fusions. These are found in many different types of pediatric cancers including sarcomas, thyroid cancer, an infantile form of kidney cancer, brain cancer, and leukemia. Patients with these tumors were also eligible for the COG clinical trial, and their results are now being analyzed. This demonstrates great potential for more research into targeted therapies that disarm genetic changes that are found across different cancer types.
There is also great potential for COG to fund and design other small studies that could have broad-reaching results.
“COG’s support of smaller trials is helping researchers get smarter about how to design trials. We’ve learned that we don’t need a large trial to find a small difference. We can use a small trial to make a big difference,” said Dr. Laetsch. “In this last trial, every single patient benefitted. That’s not very common. When that’s the case, it becomes obvious very quickly that we are on to something truly different.”
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"Targeted therapies help cure more children AND give survivors a better quality of life, so they hit both parts of the St. Baldrick’s Foundation’s mission! It’s also terrific that therapies like larotrectinib can turn out to help kids with multiple types of cancers that have the same genetic changes. All of this makes targeted therapy research an excellent investment."
Becky Chapman Weaver, Chief Mission Officer St Baldrick's Foundation |