Abstract 743P
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. Table: 743P
| Toxicity | All grades UK v GOG 0281 (%) | Grade 3-4 UK v GOG 0281 (%) |
| Skin | 79 v 92.1 | 3.6 v 15 |
| Diarrhoea | 50 v 72.4 | 3.6 v 10.2 |
| Nausea | 36 v 60.6 | 7.1 v 9.4 |
| Vomiting | 18 v 45.7 | 3.6 v 7.1 |
| Fatigue | 36 v 72.5 | 0 vs 7.9 |
| Constipation | 11 v 42.6 | 0 v 2.4 |
| Anaemia | 3.6 v 51.9 | 0 v 12.6 |
| Abdominal pain | 0 v 44.0 | 0 v 5.5 |
| Hypertension | 7.1 v 38.6 | 0 v 11.8 |
| Mucositis | 11 v - | - |
| Neurotoxicity | 11 v - | - |
| AEs of special interest | ||
| Eye | 7.1 v 2.4 | |
| Cardiac | 7.1 v 11.1 | |
| Pneumonitis | - v 2.4 |
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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
R. Shotton: Financial Interests, Personal, Sponsor/Funding: Servier. M. Randhawa: Non-Financial Interests, Invited Speaker: Bayer; Non-Financial Interests, Institutional, Other, Free drug donation: GSK. S. Williams: Financial Interests, Personal, Other, Consultancy fees: Clovis; Financial Interests, Personal, Other, Consultancy fees: GSK; Financial Interests, Personal, Funding: AstraZeneca. R.M. Glasspool: Financial Interests, Personal and Institutional, Invited Speaker, Advisory Board and Speaker fees; Site PI for commercially sponsored trials: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal and Institutional, Other, Advisory Board and Speaker fees, investigator initiated trial grant; Site PI for commercially sponsored trial: Clovis; Financial Interests, Personal, Other, Advisory Board, speaker fees and funding to attend medical conferences; Site PI for commercially sponsored trials: GSK/Tesaro; Financial Interests, Personal, Other, Consultancy fees: Sotio; Financial Interests, Personal and Institutional, Other, Advisory board; Site PI for commercially sponsored trials: Immunogen; Financial Interests, Institutional, Other, Investigator Initiated Trial Grant: Boehringer Ingelheim; Financial Interests, Institutional, Other, Investigator Initiated Trial Grant and Site PI for commercially sponsored trial: Lilly/Ignyta; Non-Financial Interests, Personal, Leadership Role: NCRI Ovarian Group; Non-Financial Interests, Personal, Leadership Role: SGCTG Ovarian; Non-Financial Interests, Personal, Member: IGCS Council; Non-Financial Interests, Personal, Member: ESMO Gyn Cancer Faculty; Non-Financial Interests, Personal, Leadership Role: GCIG Meta-Analysis Group Chair; Non-Financial Interests, Personal, Leadership Role: ENGOT Early Phase; Non-Financial Interests, Personal, Advisory Board: Target Ovarian Cancer; Non-Financial Interests, Personal, Member: Horizons Study Expert Panel. C. Gourley: Financial Interests, Personal and Institutional, Research Grant: Novartis. A.R. Clamp: Financial Interests, Personal, Other, Research funding, speaker fees, advisory board: AstraZeneca; Financial Interests, Personal, Other, Speaker fees, advisory board: Clovis Oncology; Financial Interests, Personal, Other, Speaker fees, advisory board: GSK; Financial Interests, Personal, Other, Speaker fees, advisory board: Eisai. G.C. Jayson: Financial Interests, Personal, Research Grant: AstraZeneca. All other authors have declared no conflicts of interest.