Researchers from the University of Texas MD Anderson Cancer Center have reported that the MEK inhibitor trametinib reduces the risk of disease progression or death by 52% in patients with low-grade serous ovarian carcinoma. The findings from this study were recently published in The Lancet.
The MAP kinase pathway is characteristically altered in patients with low-grade serous ovarian cancer (SOC), resulting in reduced sensitivity to chemotherapy. In a phase II/III study, the efficacy of MEK inhibitor trametinib was compared with standard of care chemotherapy.
The randomised, international, multicenter phase II/III trial enrolled 260 patients (18 years or older) with recurrent low-grade SOC from 84 hospitals across the United States and the United Kingdom. The patients were randomly (1:1) assigned to receive either oral trametinib (once daily) or one of the standard-of-care options, including paclitaxel, pegylated liposomal doxorubicin, topotecan, letrozole or tamoxifen. The majority of patients on trametinib (median age, 56.6 years) was white (89%). The study’s primary endpoint was to assess progression-free survival (PFS).
At the primary analysis, a significantly longer PFS was observed for patients receiving trametinib versus those receiving standard of care therapies (13 versus 7.2 months; hazard ratio 0.48 [95%CI, 0.36–0.64]; p<0.0001). Additionally, the median PFS in patients who crossed over from standard-of-care to trametinib was 10.8 months. The most commonly observed adverse events (grade 3 or 4) in the trametinib group were skin rash (13%), anaemia (13%), hypertension (12%), diarrhoea (10%), nausea (9%) and fatigue (8%), whereas, in the standard of care arm, the AEs included abdominal pain (17%), nausea (11%), anaemia (10%) and vomiting (8%). No treatment-related mortalities were reported.
The results from the phase II/III trial demonstrate the efficacy of trametinib as a new strand of care option. Future efforts using combination therapy are ongoing.
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