FDA Approves Qinlock for Patients with Pretreated, Advanced GIST

The targeted drug Qinlock, which interferes with the activity of proteins that drive gastrointestinal stromal tumor, has been approved by the Food and Drug Administration for patients with advanced disease that has progressed despite treatment with other kinase inhibitors.

The Food and Drug Administration (FDA) has approved Qinlock (ripretinib) to treat patients with heavily pretreated, advanced gastrointestinal stromal tumor (GIST).

The targeted drug, a kinase inhibitor that interferes with the activity of the cancer-driving proteins KIT and PDGFRα, is for adults with GIST who have received prior treatment with three or more kinase inhibitors, including Gleevec (imatinib).

The approval is based on findings from the phase 3 INVICTUS trial, in which the drug led to an 85% reduction in the risk of disease progression or death compared with placebo for the target population.

"Despite the progress that has been made over the past 20 years in developing treatments for GIST, including four FDA-approved targeted therapies — imatinib in 2002, sunitinib in 2006, regorafenib in 2013 and avapritinib earlier this year — some patients don't respond to treatment and their tumors continues to progress. Today's approval provides a new treatment option for patients who have exhausted all FDA-approved therapies for GIST," Dr. Richard Pazdur, director of the FDA's Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA's Center for Drug Evaluation and Research, stated in a press release.

Results showed that the median time until disease progression was 6.3 months with Qinlock compared with 1 month for placebo. At six months, 51% of those on the novel targeted therapy had experienced no disease progression, compared with 3.2% of those taking placebo.

Additionally, there was a 64% reduction in the risk of death with Qinlock compared with placebo. The median overall survival (the length of life from the start of study treatment) was 15.1 versus 6.6 months for Qinlock and placebo, respectively, although that finding’s statistical significance was not conclusively established. The six-month overall survival rate with Qinlock was 84.3% compared with 55.9% for placebo. The 12-month overall survival rate was 65.4% for Qinlock compared with 25.9% for placebo.

Finally, the objective response rate (the proportion of patients who had a complete or partial response to treatment) with Qinlock was 9.4% compared with no responses in the placebo group. These findings were not statistically significant. The median duration of response had not yet been reached, with seven of eight patients continuing to respond at the time of the data cutoff of May 31, 2019.

Side effects were experienced by 98.8% of patients in the Qinlock arm compared with 97.7% with placebo. Serious or severe side effects that emerged during treatment were experienced by 49.4% of patients in the Qinlock group compared with 44.2% of those taking placebo.

The most common side effects in the Qinlock and placebo groups, respectively, were hair loss (51.8% versus 4.7%), fatigue (42.4% versus 23.3%), nausea (38.8% versus 11.6%), abdominal pain (36.5% versus 30.2%), constipation (34.1% versus 18.6%) and muscle pain (31.8% versis 11.6%). The most common serious or severe grade side effects in the Qinlock versus placebo groups were, respectively, anemia (9.4% versus 14%), high blood pressure (7.1% versus 0%) and abdominal pain (7.1% versus 4.7%).

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