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Trametinib improves PFS in low-grade serous ovarian or peritoneal cancer

Elaine Soliven
12 May 2020

Treatment with trametinib, an MEK inhibitor, significantly improves progression-free survival (PFS) in patients with recurrent low-grade serous ovarian or peritoneal carcinoma (LGSOC) compared with standard of care (SOC), according to a study presented at SGO 20/20.

This phase II/III trial evaluated 260 patients diagnosed with recurrent or progressive LGSOC who had >3 lines of prior therapy between February 2014 and April 2018. Participants were randomized in a 1:1 ratio to receive either trametinib 2 mg/day or physician’s choice of SOC agent, ie, weekly paclitaxel, pegylated liposomal doxorubicin, topotecan, letrozole, or tamoxifen. Patients who experienced disease progression with SOC were crossed over to receive trametinib. [SGO 20/20, abstract 42]

At a median follow-up of 31.4 months, PFS was significantly improved in the trametinib arm compared with the SOC arm (median 13.0 vs 7.2 months; hazard ratio [HR], 0.48, 95 percent confidence interval [CI], 0.36–0.64; p<0.0001).

Exploratory analysis of the 88 patients who were crossed over to trametinib therapy showed a median PFS of 10.8 months (95 percent CI, 7.3–12.0) and median objective response rate (ORR) of 15 percent (95 percent CI, 0.07–0.22) in this group.

Patients treated with trametinib also achieved a longer duration of response (median 13.63 vs 5.88 months) and overall survival (median OS 37.0 vs 29.2 months; HR, 0.75, 95 percent CI, 0.51–1.11) than those who received SOC.

There was no significant difference between treatment arms for patient-reported quality of life outcomes.

The most common grade 3 adverse events reported in the trametinib arm vs the SOC arm were gastrointestinal (27.6 percent vs 29 percent), vascular (18.9 percent vs 8.6 percent), skin (15.0 percent vs 3.9 percent), and haematologic (13.4 percent vs 9.4 percent) toxicities.

LGSOC is a rare subtype, accounting for 5–10 percent of all serous cancers and is characterized by alterations in the MAPK pathway, relative chemoresistance, and prolonged OS compared to high-grade serous carcinoma,” said study lead author Dr David Gershenson from the University of Texas MD Anderson Cancer Center in Houston, Texas, US, and co-authors.

Overall, patients with recurrent LGSOC who received trametinib therapy had significantly improved PFS and ORR, they concluded.

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Most Read Articles
3 days ago
Routinely used for treating cardiovascular diseases, statins have been shown to benefit other conditions, and new evidence suggests that using the drug at high intensity reduces the risk of hip or knee replacement, an effect that may be specific to rheumatoid arthritis.
Jairia Dela Cruz, 3 days ago
Following vegan and vegetarian diets, which offer plenty of what is good for health, has been reported to have a downside: an increased risk of depression and anxiety, especially for younger adults.
Pearl Toh, 29 Jun 2020
Having migraine during midlife appears to be associated with a higher risk of developing dementia in later life, according to a large population-based longitudinal Danish study presented at the AHS* 2020 Virtual Meeting, indicating that migraine may be a risk factor for dementia.
Roshini Claire Anthony, Yesterday

Upadacitinib may be a suitable treatment for patients with active psoriatic arthritis (PsA) who have insufficient response to non-biologic disease-modifying anti-rheumatic drugs (non-bDMARDs), according to results of the phase III SELECT-PsA-1* trial presented at EULAR 2020.