Trametinib ‘New Standard of Care’ Option for Low-Grade Ovarian Cancer


A new study looked at trametinib's effect on survival and response rates in ovarian cancer.

Trametinib (Mekinist) improved progression-free survival (PFS) and overall response rates (ORRs) among patients with low-grade ovarian cancer, potentially creating a new standard of care for those with this rare, but deadly subtype of ovarian/peritoneal cancer, according to the findings presented at the European Society for Medical Oncology (ESMO) Congress 2019.

Compared with current standard-of-care therapy, PFS was significantly improved in the trametinib arm (median, 13.0 vs. 7.2 months; HR, 0.48; 95% CI, 2.39-12.21; P<.0001). Similarly, ORR was also significantly improved in the trametinib arm, compared with standard of care (26.2% vs 6.2%; OR, 5.4; 95% CI, 2.76-12.19; P<.0001). 

“Our findings suggest that trametinib represents a new standard-of-care treatment option for women with recurrent low-grade serous carcinoma,” lead investigator David M. Gershenson, MD, from The University of Texas MD Anderson Cancer Center in Houston, said during his presentation of the data. 

In the phase II/III study, 260 patients enrolled between February 2014 and April 2018 were randomized 1:1 to receive either 2 mg trametinib daily or 1 of 5 standards of care – including weekly paclitaxel, (Abraxane) pegylated liposomal doxorubicin, topotecan (Hycamtin), letrozole (Femara), or tamoxifen (Soltamox) – until disease progression. With this, patients initially treated with standard of care were allowed to cross over to treatment with trametinib.

The primary objective was PFS, while secondary endpoints included toxicity, quality of life, and ORR. Exploratory objectives were OS, and PFS and ORR after crossover.

In addition to their primary findings, response duration was prolonged at 13.6 months in the trametinib arm (95% CI, 8.08-18.76), compared with 5.9 months with standard of care (95% CI, 2.76-12.19). OS was also improved with trametinib (37 months; 95% CI, 30.3-NE), compared with standard of care (29.2 months; 95% CI, 23.5-51.6).

In total, 88 patients crossed over from standard of care to treatment with trametinib, for which median PFS was 10.8 months (95% CI, 7.3-12.0), with an ORR of 15% (95% CI, 0.07-0.22).

Grade 3 or higher adverse events in the trametinib and standard of care arms included hematologic toxicity (13.4% vs 9.4%, respectively), gasotrintestinal toxicity (27.6% vs 29%), skin toxicity (15% vs 3.9%), and vascular toxicity (18.9% vs 8.6%). 

The University of Edinburgh Nicola Murray Centre for Ovarian Cancer Research was a partner with the MD Anderson Cancer Center on the work.

“Low-grade serous ovarian cancer is different from other ovarian cancers because it affects younger women and is often resistant to chemotherapy,” said Charlie Gourley, clinical director of the CRUK Edinburgh Centre and director of the Nicole Murray Centre for Ovarian Cancer Research at the University of Edinburgh. “This is the first positive, randomized trials in this disease and represents a major breakthrough for patients with this type of ovarian cancer.” 


Gershenson GA, Miller A, Brady W, et al. A Randomized Phase II/III Study to Assess the Efficacy of Trametinib in Patients with Recurrent or Progressive Low-Grade Serous Ovarian or Peritoneal Cancer. Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394.

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