Real-world outcomes in patients treated with trametinib for low grade serous ovarian carcinoma

Abstract

Background In the UK, trametinib (T) is recommended for the treatment of recurrent or progressive low grade serous ovarian cancer (LGSOC) following endocrine therapy (ET) and at least one platinum (Plat) based chemotherapy (ChT) regimen, as an alternative to cytotoxic ChT under interim COVID-19 arrangements. Methods We conducted a multicentre retrospective study of patients (pts) treated with T in the UK. Eligible pts were adults with recurrent LGSOC who commenced T prior to November 2020. Results Twenty-eight pts were included (median age 53.5, 19-75). 93% had stage 3-4 disease at presentation. Prior to commencing T, pts received a median of 1.5 lines of ChT (range 0-8) and 1 line (0-3) of ET. Four pts had received ?3 lines of ChT. Thirty-six per cent had platinum resistant disease (relapse <6 months from last Plat ChT). Median follow up from start of T was 7.1 months (m). Median duration of treatment was 5.0m. Best response was partial response (PR) in 21%, stable disease (SD) in 32%, progressive disease (PD) in 36% and unavailable in 11%. 46% remain on T, 18% are on a subsequent systemic therapy and 29% have died. Treatment was stopped due to PD in 36%, at a median time of 4m. Duration of T therapy was longer in pts without prior Plat resistance (p=0.0219), though response was not significantly associated with Plat sensitivity (p=0.0716). Grade (G) 1-4 adverse events (AEs) were reported in 96% of pts (Table), with 46% experiencing ?3 AEs. G3-4 AEs occurred in 29%. There were no treatment-related deaths. The most common AEs were skin toxicity (79%), diarrhoea (50%), nausea/vomiting (54%) and fatigue (36%). Treatment was stopped due to toxicity in 5 pts 18% and dosing was interrupted in 19 pts 68%. Ten pts (36%) required a dose reduction (DR), of whom 2 required a further DR. Conclusions T is a safe and effective treatment for LGSOC, with a similar real-world response rate to that reported in GOG 0281. Low-grade toxicities were common, particularly of the skin or gastrointestinal tract, but serious toxicities were uncommon.