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

Trial ID # NCT02101788; GOG-281/LOGS
Phase III
Drug Class Signaling Pathway Inhibitors: RAS-RAF-MEK-ERK/MEK
Drug Name Trametinib
Alternate Drug Names Mekinist, MEK Inhibitor GSK1120212, JTP-74057, GSK1120212, TMT212
Drugs in Trial Letrozole, Liposomal doxorubicin, Paclitaxel, Tamoxifen, Topotecan, Trametinib
Eligible Participant

Recurrent low grade serous ovarian cancer
Patients Enrolled

260; median 2 prior therapies (1-10)
Therapy Setting

Recurrence
Study Design

Double Blind, Randomized
Endpoints

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

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)
Clinically Significant Adverse Events

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%)
Conclusion

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

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/
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