1. The median progression-free survival for trametinib was significantly greater than that for standard-of-care therapy (13 months vs. 7.2 months).
2. Anemia and skin rashes were the most common grade 3-4 adverse events associated with trametinib.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Low-grade serous ovarian carcinoma is one of five subtypes of epithelial ovarian cancers with multiple genetic mutations and poor response to platinum-based chemotherapy. Low-grade serous carcinomas are commonly associated with activating mutations in the mitogen-activated protein kinase (MAPK) pathways. Trametinib is a reversible MAPK1 and MAPK2 inhibitor that may be used in mutation-positive ovarian cancer. This randomized controlled trial aimed to evaluate the safety and efficacy of trametinib, compared to standard-of-care (one of paclitaxel, doxorubicin, topotecan, letrozole, and tamoxifen), for treatment of low-grade serous carcinoma. The primary outcome was progression-free survival, measured every 8 weeks for 15 months until disease progression or death. Key secondary outcomes included adverse events, tumor response rate, and quality of life. According to study results, trametinib resulted in a significantly longer progression-free survival compared to standard-of-care therapy with fewer progression-free survival events in the trametinib group. This study was strengthened by the assessment of all five standard-of-care groups, as opposed to only one, which adds to the validity of findings.
In-depth [randomized-controlled trial]: Between Feb 27, 2014, to Apr 10, 2018, 427 patients were assessed for eligibility across 84 hospitals in the USA and UK. Included were those ≥18 years of age with recurrent low-grade serous carcinoma and measurable disease. Altogether, 260 patients (130 in trametinib group and 130 in standard-of-care group) were included in the final analysis. The primary outcome of progression-free survival was significantly greater for trametinib (13.0 months, 95% confidence interval [CI] 9.9-15.0) compared to standard-of-care (7.2 months, 95% CI 5.6-9.9, hazard ratio [HR] 0.48, p<0.0001). Additionally, the incidence of progression-free survival events was lower in the trametinib versus standard-of-care groups, respectively (78% vs. 89%). Moreover, both groups reported mild grade 3 or 4 adverse events with skin rash (13%) and anemia (13%) prevailing in the trametinib group, and abdominal pain (17%) and nausea (11%) prevailing in the standard-of-care group. Overall, findings from this study suggest that trametinib may be considered in patients with recurrent low-grade serous carcinoma.
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