A Randomized Phase II/III Study to Assess the Efficacy of Trametinib (GSK 1120212) in Patients With Recurrent or Progressive Low-Grade Serous Ovarian Cancer or Peritoneal Cancer

Recurrent low grade serous ovarian cancer

260; median 2 prior therapies (1-10)

Recurrence

Double Blind, Randomized

ORR, DCR, DoR, PFS, OS, evaluated per RECIST

Tra (n=130) vs Standard of Care Treatment of Physician's Choice (TPC) (Let, Pac, PLD, Tam or Top)(n=130):

ORR: 26.2 (1CR, 33PR) vs 6.2% (1CR, PR) (p<0.0001)
DCR (2 months): 85 (1CR, 33PR, 77SD) vs 77% (1CR, 7PR, 92SD)
PFS: 13.0 vs 7.2  months, HR: 0.48 (0.36-0.64, p<0.0001)
DoR: 13.6  vs 5.9 months
OS: 37.6 vs 29.2 months, HR 0.76 (0.51-1.12, p=0.056)

Exploratory analysis, KRAS, NRAS and BRAF status, pre-specified chemo choice:
Tra vs TPC:
w/ KRAS, NRAS or BRAF MUT (n=44): ORR: 50.0 vs 9.1%; PFS: 13.2 vs 11.4 months, HR: 0.55 (0.28-1.07)
w/o KRAS, NRAS, or BRAF MUT (n=90): ORR: 8.3 vs 7.1%; PFS: 7.3 vs 6.3 months, HR: 0.64 (0.39-1.03)
Tra vs Let (n=87): PFS: 15.0 vs 10.6 months, HR: 0.58 (0.36-0.95, p=0.0085)
Tra vs Tam (n=54): PFS: 19.1 vs 3.7 months, HR: 0.19 (0.10-0.35)
Tra vs PLD (n=87): PFS: 11.8 vs 10.0 months, HR: 0.71 (0.44-1.17)
Tra vs Pac (n=25): PFS: 9.5 vs 5.0 months, HR: 0.47 (0.21-1.06)
Tra vs Top (n=17): PFS: 9.8 vs 3.1 months, HR: 0.22 (0.07-0.64)
w/ KRAS, NRAS or BRAF MUT vs w/o KRAS, NRAS, or BRAF MUT:
Tra: 50.0 vs 8.3%; PFS: 13.2 vs 7.3 months, HR: 0.41 (0.21-0.80)
TPC: 9.1 vs 7.1%; PFS: 11.4 vs 6.3 months, HR: 0.58 (0.30-1.10)

Tra vs TPC:
Serious AE: none
Grade 3-4 AE: anemia (13 vs 10%), skin toxicity (14 vs 1%) hypertension (12 vs 5%), abdominal pain (6 vs 17%), nausea (9 vs 11%), diarrhea (10 vs 3%)

In low grade serous ovarian cancer, trametinib therapy is associated with significantly improved ORR and PFS compared to standard of care

Gershenson DM et al. Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial. Lancet (2022) 399(10324):541-553
https://pubmed.ncbi.nlm.nih.gov/35123694/