Qinlock (ripretinib) is a targeted pill treatment for adults with advanced gastrointestinal stromal tumors (GIST) who have already been treated with at least three other drugs, such as imatinib, sunitinib, and regorafenib. It is designed for people whose cancer has become resistant to earlier therapies and can help many patients live longer and keep their disease under control, with side effects that are manageable for most.
What is GIST?
Gastrointestinal stromal tumors (GIST) are a type of cancer that starts in the wall of the digestive tract, most often in the stomach or small intestine. In the United States, about 4,000 to 6,000 people are diagnosed with GIST each year.
Most GIST tumors are driven by changes (mutations) in genes called KIT or PDGFRα. These genes act like “on switches” that tell cells to grow. When they are mutated, they can cause cancer cells to grow out of control. About 75% to 80% of GISTs have KIT mutations, and about 5% to 10% have PDGFRα mutations. Many GIST drugs, including Qinlock, are designed to block these abnormal signals.
Even with effective targeted therapies, GIST cells can develop new mutations over time, which can make the cancer resistant to treatment. When this happens, the disease may start growing again. Survival with GIST varies widely and depends on how advanced the cancer is at diagnosis and how well it responds to treatment. Reported 5‑year survival rates range from about 48% to 90%.
How Qinlock Works
Qinlock is a type of targeted therapy called a tyrosine kinase inhibitor. It was specifically designed to block a broad range of KIT and PDGFRα mutations, including many that appear after other drugs stop working. Qinlock acts as a “switch control” inhibitor—it helps turn off abnormal signals in cancer cells in multiple parts of the KIT and PDGFRα genes (for example, exons 9, 11, 13, 14, 17, and 18), including some mutations that are especially hard to treat.
For patients and caregivers, this means Qinlock may help control GIST tumors even after resistance to prior drugs has developed, offering another treatment option when other therapies have been exhausted. Qinlock is taken as a once‑daily pill. In some cases, the dose may be increased later if the cancer starts to grow again, depending on your oncologist’s advice and current guidelines.
Who Can Receive Qinlock?
The FDA has approved Qinlock for adults with advanced GIST who have already received treatment with three or more kinase inhibitors, including imatinib. Expert guidelines list Qinlock as a preferred fourth‑line treatment option for unresectable, recurrent, or metastatic GIST after imatinib, sunitinib, and regorafenib. It may also be considered if you cannot tolerate certain earlier‑line drugs.
Because GIST behaves differently from person to person, doctors usually use molecular testing (looking at KIT and PDGFRα mutations and sometimes other genes) along with your prior treatment history to decide whether Qinlock is appropriate. Your oncology team can review your biopsy results and genetic tests to see how Qinlock might fit into your overall care plan and what other options, including clinical trials, may be available.
What Did the Main Qinlock Trial Show?
The main study that led to Qinlock’s approval is called INVICTUS, a phase 3 clinical trial in people with advanced GIST who had already received imatinib, sunitinib, and regorafenib. In this study, 128–129 patients were randomly assigned to receive either Qinlock once daily or a placebo (a pill with no active drug). Patients on placebo were allowed to switch to Qinlock if their cancer progressed.
In the primary analysis, patients taking Qinlock had a median time before their cancer grew or spread of about 6.3 months, compared with about 1 month for those on placebo. Median overall survival was about 15.1 months with Qinlock versus 6.6 months with placebo. Longer‑term follow‑up and pooled analyses have shown median overall survival of around 18.2 months for people who started on Qinlock compared with about 6.3 months for those who started on placebo.
These results show that Qinlock can meaningfully extend life and delay cancer growth in people whose GIST has already been treated with several other targeted drugs. Benefits were seen across many patient subgroups, and updated analyses suggest that the survival advantage with Qinlock can persist over time with ongoing treatment and good side‑effect management.
Side Effects and Safety
Like all cancer medicines, Qinlock can cause side effects. The most common include:
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Hair thinning or hair loss (alopecia)
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Tiredness or fatigue
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Nausea or vomiting
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Abdominal pain
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Constipation or diarrhea
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Muscle or joint aches
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Decreased appetite
Many people can remain on treatment with supportive care, dose adjustments, and regular monitoring, but some may have more serious or bothersome side effects that require closer follow‑up or a change in therapy.
Long‑term safety follow‑up has shown that Qinlock’s side‑effect profile is generally consistent over time. Most side effects are mild to moderate, and relatively few patients need to stop treatment because of side effects. Your care team will typically check your skin, heart, and blood pressure and may order regular blood tests to watch for less common but more serious problems such as high blood pressure, heart issues, or severe skin reactions, as described in the full prescribing information.
Looking Ahead: More Personalized GIST Care
Over the past several years, GIST treatment has become more personalized, with new targeted drugs, more routine mutation testing, and early research on blood‑based monitoring. Qinlock and other newer therapies are helping many people with advanced GIST live longer and giving doctors more tools to match the right drug to the right tumor profile.
If you are living with GIST, you can ask your oncologist about:
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Mutation testing (including KIT, PDGFRA, SDH, and NTRK)
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Where Qinlock might fit in your treatment sequence
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Whether ctDNA (liquid biopsy) testing or clinical trials are available at your treatment center
These conversations can help you understand your options and make informed decisions about your care.
More targeted drug options
- Newer targeted therapies such as ripretinib and avapritinib have expanded options for people whose GIST has stopped responding to imatinib, sunitinib, and regorafenib. Ripretinib is now an established fourth‑line treatment for advanced GIST, and avapritinib is a key option for tumors with certain PDGFRA mutations (especially D842V), which historically were very hard to treat.
- Recent analyses have confirmed that ripretinib can provide durable disease control and meaningful survival in heavily pretreated patients, including longer‑term follow‑up from trials like INVICTUS and related studies.
More precise, mutation‑guided care
- Guideline updates now place more emphasis on doing molecular testing of the tumor (KIT, PDGFRA, SDH, NTRK and other alterations) early in the disease course, because the “driver” mutation strongly influences which drug will work best. For example, patients with NTRK fusions may receive NTRK inhibitors such as larotrectinib or entrectinib, and SDH‑deficient GIST may be treated differently from KIT‑mutated tumors.
- This shift means that many treatment decisions are no longer “one‑size‑fits‑all,” but tailored to the specific genetic features of each person’s tumor.
Blood tests (ctDNA) to guide treatment
- New research shows that liquid biopsies, which look for tumor DNA in the blood (circulating tumor DNA, or ctDNA), can detect multiple KIT mutations and track how they change over time. In studies linked to the INTRIGUE trial, ctDNA helped identify which patients did better with ripretinib versus sunitinib in the second‑line setting, based on their mutation pattern.
- These ctDNA tools are still being studied but may soon help doctors choose the most effective drug more quickly, reduce trial‑and‑error, and monitor emerging resistance without repeated tissue biopsies.
Early steps in immunotherapy and combinations
- Immunotherapy has not yet become standard for most GIST patients, but recent research is exploring how immune‑checkpoint inhibitors might work together with TKIs or in select biologic subtypes. Early studies and reviews point to a more complex immune environment in GIST and suggest that future trials may combine targeted drugs, immunotherapy, and other agents to overcome resistance.
- For patients, this means that while standard TKIs remain the backbone of care, more clinical trials are testing new combinations and novel targets, offering additional options when standard therapies no longer work.
If you are living with GIST, you can ask your oncologist about mutation testing (including KIT, PDGFRA, SDH, and NTRK), whether drugs like avapritinib or ripretinib are appropriate in your treatment line, and whether ctDNA testing or clinical trials are available at your center.
Strategies to Improve Treatment
Several new drugs and strategies are being tested in clinical trials to help people with GIST, especially when standard treatments like imatinib, sunitinib, regorafenib, avapritinib, and ripretinib stop working.
- Next‑generation KIT inhibitors such as IDRX‑42 (now called GSK6042981) are moving into larger “pivotal” studies, including a phase 3 trial comparing this drug directly with sunitinib as a possible new option for second‑line treatment.
- Other experimental tyrosine kinase inhibitors, including bezuclastinib and related agents, are being studied alone and in combinations such as sunitinib plus bezuclastinib, where top‑line results from the PEAK trial suggest this combination may better control resistant GIST.
- The INSIGHT study is comparing sunitinib with ripretinib in patients whose tumors have specific KIT exon 11 and 17/18 mutations, while another trial is testing IDRX‑42 versus sunitinib in the second‑line setting and an additional study is evaluating imatinib together with the investigational drug ziftomenib.
Many major cancer centers and clinicaltrials.gov maintain active GIST trial lists, so patients can ask their oncologist or clinical trial office whether studies of these newer drugs and combinations might be an option for their specific mutation and treatment history.
References
Blay JY, Serrano C, Heinrich MC, et al. Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 Jul;21(7):923-934. doi: 10.1016/S1470-2045(20)30168-6. Epub 2020 Jun 5. Erratum in: Lancet Oncol. 2020 Jul;21(7):e341.
www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-ripretinib-advanced-gastrointestinal-stromal-tumor. Accessed May 15, 2020.
