Qinlock Becomes Preferred Second-Line Drug for GIST Subset

The National Comprehensive Cancer Network (NCCN) updated its Clinical Practice Guidelines in Oncology to state that Qinlock (ripretinib) is the preferred second-line treatment for patients with gastrointestinal stromal tumors (GIST) who are intolerant to Sutent (sunitinib), according to a press release from Deciphera Pharmaceuticals, the manufacturer of Qinlock.

The NCCN is an organization made up of experts from more than 30 cancer centers across the United States. It is dedicated to improving cancer care through, among other things, their guidelines, which outline evidence-based treatments for individual types of cancer.

Qinlock works by inhibiting certain KIT mutations, as well as the primary exon 17 D816V mutation, which are involved in the occurrence of GIST, a type of cancerous tumor that is found in the gastrointestinal tract.

“The inclusion of Qinlock in the latest NCCN clinical practice guidelines underscores both the need for additional treatment options for GIST patients in the post-(Gleevec [imatinib]) setting and the significance of the results from the INTRIGUE study, which demonstrated that Qinlock is an active and well-tolerated agent,” Steve Hoerter, president and chief executive officer of Deciphera Pharmaceuticals, said in the release.

The phase 3 INTRIGUE study, which led to the guideline update, included patients with advanced GIST who were previously treated with Gleevec and were not eligible for treatment with Sutent. Participants were randomly assigned to receive either Qinlock or Sutent.

Findings showed that there was no statistically significant difference in progression-free survival (time from treatment until t he disease worsens) between the two groups, though Qinlock tended to be better tolerated. In particular, fewer patients experienced severe (grade 3/4) side effects with Qinlock compared with Sutent (41.3% versus 65.6%).

Additionally, patients who were receiving Sutent were three times more likely to develop grade 3 hypertension (high blood pressure) than those receiving Qinlock (26.7% versus 8.5%, respectively) and seven times more likely to experience grade 3 hand-foot syndrome (10% versus 1.3%).

Patients in the Qinlock group also reported less decline in their ability to engage in work and other activities during treatment, and fewer patients on Qinlock also experienced moderate to extremely large impact on their lives due to skin-related side effects.

Based on these findings, the Food and Drug Administration (FDA) also granted a Breakthrough Therapy Designation to Qinlock to treat adults with unresectable (ineligible for surgical removal) or metastatic (spread to other parts of the body) GIST who were previously treated with Gleevec and have a KIT exon 11 mutation and co-occurring KIT exon 17 and/or 18 mutations.

Of note, a Breakthrough Therapy Designation helps speed up the development and FDA review of therapies that treat serious diseases or conditions.

“If approved, we believe Qinlock has the potential to become the standard-of-care for this group of second-line GIST patients around the world,” Hoerter said in the release. “GIST key opinion leaders and physicians have long been proponents of clinical drug development targeted at specific molecular subtypes of GIST, and we are pleased with the FDA’s recognition that the (circulating tumor) DNA data indicates Qinlock may demonstrate substantial improvement over the current standard-of-care in this population.”

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