WAYNE, New Jersey — Forty years ago, Karen Meyers of Melville, New York, had surgery to remove an encapsulated tumor near her stomach. She was diagnosed with gastrointestinal stromal tumor (GIST) by an oncologist with minimal knowledge of this rare disease, and without further testing was immediately put on imatinib mesylate (Gleevec®). 

But Meyers got worse instead of better; she soon realized that her doctors had made a serious mistake.

“I don’t know what made me uncomfortable — maybe working in health care for people with developmental disabilities, or the comment from a doctor friend many years before about the importance of second opinions,” said Meyers, speaking June 28, 2021, at the 2021 Rare Impact Awards, a virtual event hosted by the National Organization of Rare Disorders (NORD).

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A contact at NORD referred her to the nonprofit Life Raft Group, which is dedicated to GIST patients. The group’s experts put her in touch with Robert Maki, MD, PhD, a medical oncologist specializing in GIST. He, in turn, diagnosed her with a rare form of unresectable, or metastatic, GIST driven by a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation known to be resistant to imatinib mesylate. She was told about a promising clinical trial for BLU-285, an experimental therapy being developed by Blueprint Medicines in Cambridge, Massachusetts.

“I followed the progress of that trial, and when I met Jim Baker [Blueprint’s senior vice president of corporate affairs] at the 2018 Life Fest in Miami, I even offered to switch from being a lifelong Yankees fan to a Red Sox fan if I needed to [in order to] join the trials,” she joked.

Meyers entered the trial, whose eventual success led to the US Food and Drug Administration’s Jan. 9, 2020, approval of avapritinib (Aykavit™) — a drug she attributes to adding years to her life.

“My last MRI showed no evidence of disease,” she said. “Now I am hopeful, looking forward to watching my grandchildren grow up.”

Blueprint received a 2021 Industry Innovation Award from NORD at the Rare Impact Awards event. In accepting the award on behalf of the company, chief operating officer Kate Haviland said cancer is fundamentally a genetic disease.

“This provides the opportunity for us to understand the genetic root cause driving cancer, and to develop drugs which specifically target those root causes,” Haviland said. “From the outset, we believe by taking this unique approach, we could work to improve patient outcomes by developing the right drug, for the right patient, at the right time.”

Peter Knox, senior research director at Life Raft Group. Credit: Larry Luxner

Peter Knox, senior research director at Life Raft Group, said GIST is the most common among sarcomas, which represent 1% of all cancers; some 5000 Americans are newly diagnosed each year with the disease.

“Many people have what we call micro-GISTs, which are GISTs less than 2 centimeters. Those GISTs never evolve into full-blown GISTs,” Knox said in a recent interview. “We don’t understand why that is. We’re beginning to understand now. We used to say that if a GIST was under 2 centimeters there’s really nothing to worry about. But we’ve actually seen cases now where those GISTs do extrapolate to become larger and more problematic.”

Life Raft Group was established by Norman Scherzer, a former New York City assistant health commissioner. In the late 1990s, his wife, Anita, was misdiagnosed with leiomyosarcoma, a rare type of cancer that begins in smooth muscle tissue such as the abdomen or uterus. She actually had GIST, which at the time had no treatment options.

“It turned out, just luckily, that at that time there was a drug in trial called STI-571, which eventually became Gleevec, and was approved,” Knox said. “Anita got in the trial and she responded extremely well, as did many patients who literally walked out of their deathbeds.”

That led Scherzer to form the group during the early trials of imatinib mesylate. The group was formally incorporated in 2002; Scherzer is still involved.

“We work with many of those companies to basically help after the drug is approved, but now at this time, we got involved well earlier than that, in the early stages,” he said. “At our heart, we’re an advocacy organization that supports patients through education, research, and outreach. And we also educate doctors as well, because how common is it for a doctor to see GIST?  The reality is, for the average community physician, not very common — once or twice in your career. We tend to help patients get routed to experts whenever possible.”

At present, three TKI (tyrosine kinase inhibitor) therapies are available for GIST patients with no specific mutations: imatinib mesylate (developed by Novartis as Gleevec but now sold also as a generic), Pfizer’s sunitinib (Sutent®), and Bayer’s regorafenib (Stivarga®). In addition, Deciphera recently won FDA approval for ripretinib (Qinlock™) specifically for advanced GIST patients who have received 3 or more prior treatments for their disease.

“It’s now very common to hear about cancer being classified not by location, but instead by the actual biological mutation in the genes,” Knox said. “This has been happening with GIST since the very beginning. When Gleevec was approved back in the early 2000s, it was actually approved for [GISTs related to the KIT protein]. Our most common mutations are exon 11 or exon 9, and those are mutations in KIT. Since then, many other mutations have been found.”

Knox added: “The last generation of drugs approved [for GIST] are very specific and targeted to these actual sub-mutations, which is a good thing, I think, going forward.”