Mektovi Fails to Improve Progression-Free Survival in Rare Ovarian Cancer Subset, But Shows Effective Results

September 10, 2020
Conor Killmurray

Compared to physician’s choice of chemotherapy, the MEK inhibitor Mektovi failed to improve progression-free survival in patients with low-grade serous ovarian carcinomas. However, the study authors note Mektovi demonstrated promising results that support continued use of the treatment.

While a study comparing the mitogen-activated protein kinase (MEK) inhibitor Mektovi (binimetinib) to physician’s choice of chemotherapy to treat patients with low-grade serous ovarian carcinomas (LGSOCs) did not meet its primary endpoint of improving progression-free survival, researchers suggest the data demonstrate Mektovi was active enough to merit its use as a treatment for this patient population.

In research published in the Journal of Clinical Oncology, investigators looked at a total of 303 patients with LGSOC who were randomly assigned a twice daily regimen of Mektovi or their physician’s choice of chemotherapy (PCC). Eligible patients in the study had recurrent disease and had received one to two prior platinum-based chemotherapy treatments for their cancer. Using a blinded independent central review, the main goal of the study was to measure progression free survival (PFS), which is the time a patient’s cancer does not progress during or after treatment.

At the time of the review, the median PFS for Mektovi was 9.1 months and 10.6 months in PCC. This difference was not significant, according to the study authors, moreover other endpoints were similar between the two arms. For example, the overall response rate was 16% in the Mektovi arm compared to 13% in the PCC arm and the duration of response was 8.1 months compared to 6.7 months, respectively.

However, these endpoints were higher and more consistent than researchers had previously anticipated, especially in the chemotherapy arm. Median overall survival observed was 25.3 months in the Mektovi arm versus 20.8 months for patients receiving PCC. At the data cutoff date, 23 patients in the Mektovi group and nine patients in the PCC group had ongoing responses to treatment.

“The median (overall survival) for patients with advanced LGSOC approaches 10 years, with patients often experiencing significant morbidity from their disease during that time,” the authors wrote, explaining the importance of the outcome of this study even as it missed its main goal. “Currently, treatment options are limited for patients with this disease and few offer objective decreases in disease burden or delays in tumor progression.”

In the study, researchers also detected 47 mutations in at least 5% of patients. Of those patients, 33% had the KRAS mutation with an even distribution in both arms of the study and was identified in 46 patients in the Mektovi arm and in 24 patients treated with PCC. Of the patients in the Mektovi arm, the KRAS mutation had a significant association with response to treatment of Mektovi but not with PCC.

This association extended to prolonged PFS, as patients with the mutation had a PFS of 17.7 months and those with the wild type mutation had a PFS of 10.8 months. This was not observed in PCC, suggesting that the KRAS mutation is a biomarker for response in patients with LGSOC treated with Mektovi.

“Additional exploration is warranted to determine if patients with KRAS mutation may derive greater benefit from binimetinib,” the authors wrote. “Although KRAS has been an elusive target across multiple cancer types, prior early-phase studies have found promising response rates to MEK inhibitors and MEK inhibitor combinations in those patients with KRAS-mutant LGSOC.”

Even though Mektovi failed to improve PFS compared to PCC, the authors note that the results of the trial are still promising.

“Although the MILO/ENGOT-ov11 trial did not meet its primary end point, (Mektovi) did display a clinically meaningful PFS and ORR and, therefore, should be considered a viable treatment option in this setting,” they concluded.

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