ESMO 2019 — Trametinib tackles chemoresistance in recurrent/progressive low-grade serous ovarian or peritoneal cancer

  • Cristina Ferrario — Agenzia Zoe
  • Oncology Conference reports
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  • Compared with physician’s choice standard of care (SOC), trametinib significantly improved progression-free survival (PFS) and objective response rate (ORR) in patients with recurrent low-grade serous carcinoma of the ovary/peritoneum (LGSOC).
  • Adverse events (AE) were mostly relatively minor, but not negligible.

Why this matters

  • LGSOC is characterised by alterations in the MAPK pathway and is chemoresistant.
  • ORR is only 5% after recurrence.
  • New effective therapies are needed.

Study design

  • Phase 2/3 trial on 260 patients with LGSOC (48.1% with ≥3 prior lines of therapy).
  • 1:1 randomisation to either trametinib or 1 of 5 SOC options (paclitaxel, pegylated liposomal doxorubicin, topotecan, letrozole, tamoxifen) until disease progression.
  • Crossover to trametinib was allowed in case of progression on SOC.
  • Primary endpoint: PFS superiority of trametinib vs SOC.
  • Included secondary endpoints: toxicity, quality of life, ORR by RECIST 1.1.
  • Exploratory endpoints: OS, PFS, and ORR after crossover.
  • Funding: National Cancer Institute (US); Novartis.

Key results

  • Trametinib significantly improved PFS compared with SOC (HR 0.48; P
  • Higher ORR was reached with trametinib (26.2%) vs SOC (6.2%) (OR 5.4; P
  • Response duration was 13.63 months and 5.88 months, respectively, with trametinib and SOC.
  • Median OS was 37.0 months with trametinib vs 29.2 months with SOC (HR 0.75; P
  • Median PFS was 10.8 months and ORR was 15% for women who crossed over to trametinib (n=88).
  • Main grade ≥3 adverse events in trametinib vs SOC included hematologic (13.4% vs 9.4%), GI (27.6% vs 29%), skin (15% vs 3.9%), and vascular toxicity (18.9% vs 8.6%).

Expert commentary

  • “Trametinib led to improvements in PFS not seen with other MEK inhibitors. We now need to know how to manage toxicities and when to use the drug,” said Jonathan Ledermann, UCL Cancer Trials Centre, UCL Cancer Institute, London, United Kingdom, who was not involved in the study.