The combination of imatinib and binimetinib in patients with succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) showed promising results, according to a new phase 1b clinical trial (NCT01991379).

“The combination of imatinib and binimetinib is safe with manageable toxicity and has encouraging
activity in SDH-deficient but not imatinib-refractory KIT/PDGFRA-mutant GIST,” the study authors said.

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The clinical benefit rate for the SDH-deficient GIST patients was 100% (95% CI, 39.8-100) at 12 months. It decreased to 75% (95% CI, 19.4-99.4) and 50% (95% CI, 6.8-93.2) at 18 and 24 months, respectively.

The median progression-free survival was 45.1 months (95% CI, 15.8-not estimatable). Most (75%) participants remained progression-free at 18 months, while half remained progression-free at 24 months.

The authors were unable to estimate the median overall survival after treatment for patients with SDH-deficient GIST, but 83.3% and 66.7% were alive at 18 and 36 months, respectively.

Overall, 2 serious treatment-associated adverse events were reported in 2 participants: a grade 2 dropped head syndrome and a grade 3 central retinal vein occlusion. Both events required discontinuation of therapy, but the participants recovered fully.

Among the most commonly observed treatment-associated toxicities were asymptomatic creatinine phosphokinase elevation, increases in aspartate aminotransferase and alanine aminotransferase, anemia, decreases in white blood cell and platelet counts, acneiform and maculopapular rashes, hypophosphatemia, hypocalcemia, hypomagnesemia, diarrhea, nausea, vomiting, and peripheral, facial, and periorbital edemas.

Currently, there are no standard of care therapeutic options for advanced SDH-deficient GIST. “Unlike KIT/PDGFRA-mutant GIST, SDH-deficient GIST confers primary resistance to imatinib, the first-line standard-of-care systemic therapy in advanced GIST. They are also relatively insensitive to other tyrosine kinase inhibitors,” the authors wrote. Therefore, these results are encouraging.

References

Chi P, Qin LX, Camacho N, et al. Phase Ib trial of the combination of imatinib and binimetinib in patients with advanced gastrointestinal stromal tumors (GIST). Clin Cancer Res. Published online February 2, 2022. doi:10.1158/1078-0432.CCR-21-3909

MEK162 in combination with imatinib mesylate in patients with untreated advanced gastrointestinal stromal tumor (GIST). ClinicalTrials.gov. November 25, 2013. Updated November 4, 2021. Accessed February 9, 2022.