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Home»Health»Doctors find melanoma drugs effective against rare brain cancer
Health

Doctors find melanoma drugs effective against rare brain cancer

July 14, 2023No Comments6 Mins Read
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Doctors find melanoma drugs effective against rare brain cancer
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By going down to the molecular level, doctors have uncovered a way to treat tumors caused by a rare brain cancer using medicines that already exist.

Two cancer drugs — currently approved for the treatment of melanoma — were able to treat a rare type of brain cancer called PCP, or papillary craniopharyngioma, researchers reported in a study published Thursday in the New England Journal of Medicine.

In a small clinical trial, 16 patients with PCP who had not received any prior radiation therapy were given cancer drugs that target the proteins BRAF and MEK, which are both involved in cell growth. The drugs — vemurafenib and cobimetinib, both marketed by Genentech — turned out to be incredibly effective, and tumors shrank by over 90% on average.

“The results of this trial really do represent the highest response rate to date of systemic therapy in brain tumors. So we were very pleasantly surprised, and these types of responses are actually unprecedented,” said Priscilla Brastianos, lead author of the study and director of the Central Nervous System Metastasis Center at the Mass General Cancer Center.

This study is the first to show that medical therapies can have such a dramatic effect on brain tumors. Not only will it significantly help patients with PCP, but it might also encourage the field of neuro-oncology to invest more research efforts to advance precision medicine for brain cancer management.

Ian Watson, an associate professor in the department of biochemistry at McGill University and member of the Goodman Cancer Institute, said that “the tumor shrinkage was incredibly impressive.” Watson is familiar with BRAF mutations in melanoma and was not involved in the study. “The fact that no patients developed progressive disease while on therapy was incredibly promising,” he said.

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The current standard of care to treat PCPs is surgery and targeted radiation. However, to Brastianos, these approaches can be associated with significant side effects. These tumors often exist next to critical brain and vascular structures, so “patients can have lifelong complications” from surgery and radiation, Brastianos said. “That’s what makes treating these tumors very challenging, [and] what inspired us to try to find better treatments for this disease.”

Michael Glantz, a professor of neurosurgery and oncology at Pennsylvania State University who was not involved in the study, said that surgery and radiation “is frequently effective, but with equal frequency is pretty morbid.” Surgery and radiation can impair vision, intellectual function, and sleep, and dysregulate hunger, among other consequences.

To find a better treatment, Brastianos, who is an associate professor of medicine at Harvard Medical School, wanted to study PCP at the molecular level. She worked with Sandro Santagata, an associate professor of pathology at Brigham and Women’s Hospital, to genetically sequence the tumors of patients with PCP, and found that one specific mutation to the BRAF gene was present in 95% of patient tumors. Fortuitously, this same mutation happened to also be quite common in melanoma.

“Very fortunately for these patients, we stumbled upon a mutation for which therapies had just recently … gotten FDA approved for melanoma,” Santagata said. This “allowed us to then try to transfer them” to PCP, he said.

Since there are no existing animal models for PCP, Brastianos and Santagata were able to test their hypothesis directly in humans.

In accordance with protocols approved from the institutional review board at the Dana Farber/Harvard Cancer Center, Brastianos delivered the drugs approved for melanoma to a patient with PCP who had given informed consent for research studies.

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“Within two years of that laboratory discovery, we then treated a patient with an aggressive [PCP],” Brastianos said. The patient responded remarkably well to the melanoma drugs; his brain tumor shrank by 85% in just 35 days.

Encouraged by this single case, Brastianos and Santagata embarked on a larger clinical trial, the results of which are reported in the new study. As a pre-planned standard of care, patients had the option to undergo surgery and radiation after completing their cancer drug treatment. Notably, seven patients abstained from this option, and six of those showed no evidence of tumor progression after an average of around two years.

Ted Schwartz, a professor of neurosurgery familiar with PCP at Weill Cornell Medicine who was not involved in the study, said that while the trial results are “remarkable,” there are a couple of significant caveats. Specifically, 14 patients suffered serious side effects during treatment, and PCP did progress in three patients after treatment was stopped.

Both Brastianos and Schwartz said that several unanswered questions remain, including optimizing the duration of treatment, finding out how long it can prevent disease progression after treatment is stopped, and how it will fit into the existing models of care with surgery and radiation.

The results of this study were made possible by the comprehensive sequencing of individual tumors, a feat central to the ethos of precision medicine. This emerging approach, as it relates to cancer, allows doctors to tailor treatment plans around individual patients based on their cancer’s biology.

In the world of brain tumors, this is becoming the standard of care. “Every brain tumor that gets removed is sent for detailed molecular typing and characterization to try to see if there’s a targetable mutation that can be used to treat that tumor,” Schwartz said. “And that’s really characteristic of the precision medicine era that we’ve entered.”

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The remaining challenges to the ubiquitous use of precision medicine lie in both the cost of performing and analyzing whole genome sequencing, and the relative scarcity of targeted cancer therapies that exist today.

“In the absence of insurance, these big panels of molecular tests are just staggeringly expensive,” Glantz said. While the cost of sequencing itself is relatively affordable at just several hundred dollars in 2023, meaningful analysis of the sequencing can be pricey. A study in 2017 found that whole genome analysis for cancer patients cost on average over $26,000, while another one in 2018 found the cost to range from $1,906 to $24,810.

“The other problem is that … you do all of these tests, and you don’t find actionable mutations that correlate with the treatments that we have,” Glantz said. Schwartz agreed, saying that “the need now is to find more immunotherapies and monoclonal antibodies to target these different mutations” uncovered by genome sequencing.

According to Watson, efforts should be made towards reducing cost and increasing availability of whole genome sequencing, identifying more mutations or “biomarkers” responsible for cancer pathology, and developing more therapies to target them.

For now, the success observed in treating PCP presents a strong case for using precision medicine to treat other rare brain cancers with existing therapies.

“For rare [brain] tumors, where you’re dealing with a few hundred patients a year … it’s hard to develop a whole new line of therapy for them,” Santagata said. “This is one way forward for patients with those rare, rare diseases.”

Brain Cancer Doctors drugs Effective find Melanoma rare
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