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.
Gershenson DM, Miller A, Brady WE, Paul J, et al. Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial. Lancet. 2022 Feb 5;399(10324):541-553.