A novel agent for recurrent low-grade serous ovarian carcinoma
Low-grade serous carcinoma is a histologic subtype that makes up approximately 5% of all epithelial ovarian cancers.3 Patients with low-grade serous carcinoma are often younger and, because of the indolent nature of the histology, generally have a longer overall survival compared with patients with high-grade serous carcinoma. Unlike high-grade disease, however, low-grade serous carcinoma usually is resistant to chemotherapy, making treatment options limited for patients with advanced and recurrent disease.
Trametinib: A potential option
In an international, randomized, open-label trial (GOG 281/LOGS), Gershenson and colleagues investigated the efficacy of trametinib compared with standard-of-care chemotherapy in patients with recurrent low-grade serous ovarian cancer.4 Trametinib, a mitogen-activated protein kinase MEK inhibitor, is a targeted agent that is FDA approved for treatment in BRAF-mutated melanoma, lung, and thyroid cancers.
Patients with recurrent low-grade serous ovarian cancer were randomly assigned to trametinib (n = 130) or 1 of 5 standard-of-care treatment options (n = 130), including both chemotherapy and hormonal treatments. Those assigned to trametinib were significantly less likely to have disease progression (78% vs 89%), with a median progression-free survival of 13 months, compared with7.2 months in controls (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36–0.64). Additionally, patients who had a radiographic response to trametinib experienced a longer duration of response compared with those who responded to standard-of-care treatment (13.6 months vs 5.9 months).
While there was no statistically significant difference in overall survival (HR, 0.76; 95% CI, 0.51–1.12), crossover to trametinib from the standard-of-care group was allowed and occurred among 68% of patients, which limits the study’s ability to measure differences in overall survival.
Trametinib was well tolerated by patients, but skin rash and anemia followed by hypertension were the most common adverse effects. In the standard-of-care group, the most common toxicities were abdominal pain, nausea, and anemia. A slightly higher proportion of patients in the trametinib group discontinued the drug due to toxicity compared with the standard-of-care group (36% vs 30%), but the there was no difference between the 2 groups in scores on quality-of-life assessments.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
Although trametinib is not yet FDA approved for the treatment of ovarian cancer, the National Comprehensive Cancer Network has added trametinib as a treatment option for recurrent low-grade serous ovarian carcinoma, given the significant improvement in progression-free survival compared with standard-of-care treatment.
Although trametinib is not yet FDA approved for the treatment of ovarian cancer, the National Comprehensive Cancer Network has added trametinib as a treatment option for recurrent low-grade serous ovarian carcinoma, given the significant improvement in progression-free survival compared with standard-of-care treatment.
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