Dr. Grisham on MEK Inhibition in Low-Grade Serous Ovarian Cancer

Rachel N. Grisham, MD
Published: Tuesday, Feb 26, 2019



Rachel N. Grisham, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses MEK inhibition in the treatment of patients with low-grade serous ovarian cancer.

The GOG-239 study was the first prospective clinical trial performed in this setting, Grisham says. For the trial, investigators evaluated the use of single-agent selumetinib, a MEK inhibitor, for the treatment of patients with recurrent low-grade serous ovarian cancer, and the response rate was promising at 15%. In that trial, there was also molecular analysis to assess if patients with KRAS and BRAF mutations were more likely to benefit from treatment. However, Grisham notes, only a small number of patients had molecular results available; as such, investigators were unable to find an association between molecular alteration and response to treatment. Moving forward, newer modalities such as next-generation sequencing may allow for researchers to make these determinations.

Following the results of GOG-239, there have been subsequent studies looking at MEK inhibition in this patient population. There is an ongoing phase III GOG study of trametinib (Mekinist) versus physician’s choice of chemotherapy or hormonal therapy, which has finished accruing but results are not yet available. There was also a study of binimetinib (Mektovi), a single-agent MEK inhibitor, versus physician’s choice of chemotherapy in this patient population. That study was stopped after enrolling over 300 patients, as it crossed a predefined futility endpoint for the hazard ratio for progression-free survival. However, adds Grisham, the results of the study were interesting and will be published soon.
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Rachel N. Grisham, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses MEK inhibition in the treatment of patients with low-grade serous ovarian cancer.

The GOG-239 study was the first prospective clinical trial performed in this setting, Grisham says. For the trial, investigators evaluated the use of single-agent selumetinib, a MEK inhibitor, for the treatment of patients with recurrent low-grade serous ovarian cancer, and the response rate was promising at 15%. In that trial, there was also molecular analysis to assess if patients with KRAS and BRAF mutations were more likely to benefit from treatment. However, Grisham notes, only a small number of patients had molecular results available; as such, investigators were unable to find an association between molecular alteration and response to treatment. Moving forward, newer modalities such as next-generation sequencing may allow for researchers to make these determinations.

Following the results of GOG-239, there have been subsequent studies looking at MEK inhibition in this patient population. There is an ongoing phase III GOG study of trametinib (Mekinist) versus physician’s choice of chemotherapy or hormonal therapy, which has finished accruing but results are not yet available. There was also a study of binimetinib (Mektovi), a single-agent MEK inhibitor, versus physician’s choice of chemotherapy in this patient population. That study was stopped after enrolling over 300 patients, as it crossed a predefined futility endpoint for the hazard ratio for progression-free survival. However, adds Grisham, the results of the study were interesting and will be published soon.



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