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Imatinib Plus Binimetinib Found Effective With Manageable Toxicity in Advanced GIST
The results of a phase 2 trial, which evaluated the efficacy and safety of imatinib plus binimetinib in first-line treatment of advanced gastrointestinal stromal tumor (GIST), warranted the comparison of the novel strategy of imatinib as a single agent. The strategy targeted GIST lineage-specific master regulators ETV1 and KIT by MEK and KIT inhibitors, with the goal of achieving synergy. (J Clin Oncol, published online January 18, 2022: DOI: 10.1200/JCO.21.02029).
“Despite the clinical success of imatinib, most patients with advanced (GIST) develop resistance to imatinib and succumb to their disease. We aim to identify a therapeutic strategy that can enhance the efficacy of imatinib in frontline treatment of GIST,” explained lead author Ping Chi, MD, PhD, Memorial Sloan Kettering Cancer Center, alongside fellow investigators.
In the study, 42 treatment-naive adult patients received imatinib (400 mg once daily) plus binimetinib (30 mg twice daily) in 28-day cycles between September 15, 2014, and November 15, 2020.
The primary end point was stated as the most prominent objective response rate (ORR), as measured by RECIST1.1 criteria (including complete and partial responses). Of the 42 patients, 29 had a partial response, while 39 had a Choi partial response of about 8 weeks. The best ORR was 69.0% (two-sided 95% CI, 52.9 to 82.4). Median progression free survival (PFS) was 29.9 months (95% CI, 24.2 to not estimable). Five of 8 patients with locally advanced disease underwent surgery after the dual therapy, and achieved significant pathologic response (≥ 90% treatment effect). There were no unexpected toxicities, according to the abstract.
“To our knowledge, this is the first trial testing a tyrosine kinase inhibitor combination in the frontline treatment of GIST. The combination of imatinib and binimetinib is effective with manageable toxicity,” concluded Chi and co-investigators. -Alexis Hyams
