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Avapritinib vs Other Tyrosine Kinase Inhibitors for PDGFRA D842V–Mutated Gastrointestinal Stromal Tumors


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Data from a study published by Margaret von Mehren, MD, and colleagues in BMC Cancer showed that avapritinib, a platelet-derived growth factor receptor A (PDGFRA) inhibitor, has a “clinically meaningful benefit” for the treatment of gastrointestinal stromal tumors (GIST) with PDGFRA D842V mutations.

PDGFRA mutations occur in about 10% to 15% of GISTs, and D842V is the most common PDGFRA mutation.

Margaret von Mehren, MD

Margaret von Mehren, MD

“Until the U.S. Food and Drug Administration approval of avapritinib, we did not have a drug that was effective against this mutation,” said Dr. von Mehren, Chief of the Division of Sarcoma Medical Oncology and Professor in the Department of Hematology/Oncology at Fox Chase Cancer Center. “If these patients had their disease return, we had no real therapeutic options apart from attempting surgery or enrolling in a clinical trial.”

Avapritinb vs Other Tyrosine Kinase Inhibitors

The research team conducted the retrospective study in patients with unresectable or metastatic GISTs with PDGFRA D842V mutations and compared their outcomes to those enrolled in the recently published NAVIGATOR trial. They compared the efficacy of avapritinib with that of several other previously approved tyrosine kinase inhibitors that have been shown to lack activity against this mutation.

KEY POINTS

  • The median overall survival for patients treated with avapritinib was not reached; patients treated with other tyrosine kinase inhibitors had a median overall survival of 12.6 months.
  • The overall survival rate at 6 and 48 months was 100% and 63% for avapritinib and 56% and 17% for the other tyrosine kinase inhibitors.
  • Adjusted and unadjusted progression-free survival rates were also longer for patients treated with avapritinib.

The study included 56 patients treated with avapritinib in the NAVIGATOR trial and 19 patients treated with other tyrosine kinase inhibitors. The median overall survival for patients treated with avapritinib was not reached; patients treated with other tyrosine kinase inhibitors had a median overall survival of 12.6 months.

The overall survival rate at 6 and 48 months was 100% and 63% for avapritinib and 56% and 17% for the other tyrosine kinase inhibitors. Adjusted and unadjusted progression-free survival rates were also longer for patients treated with avapritinib.

“We are never going to be able to do a randomized trial in patients with this specific mutation because it occurs in such a small number of patients and because information suggests that these other drugs do not work,” said Dr. von Mehren. “This study was another way to provide context to the outcomes we are seeing with avapritinib.”

She said that in the most recently published NAVIGATOR results, the median progression-free survival was nearly 3 years, and the median overall survival was not yet reached.

“Our data demonstrated that there is truly a clinically meaningful benefit to this drug compared with the benefit derived from other drugs, even among what is likely a group of patients with potentially more severe disease,” said Dr. von Mehren.

Even acknowledging some of the limitations inherent in a retrospective study, this analysis should help confirm that avapritinib provides meaningful, durable disease control for patients with GISTs and PDGFRA D842V mutations.

Disclosure: For full disclosures of the study authors, visit bmccancer.biomedcentral.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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