GOG 281/LOGS
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
Phase 2/3N = 260NCT02101788
- Population
- Recurrent low-grade serous carcinoma of the ovary or peritoneum with measurable disease; serous borderline tumours and mixed low-/high-grade tumours excluded; unlimited prior regimens
- Design
- International, randomised, open-label phase 2/3 trial at 84 hospitals in the USA and UK. Patients with recurrent low-grade serous carcinoma and measurable disease, at least one prior platinum-based regimen, were randomised 1:1 to oral trametinib 2 mg once daily or one of five standard-of-care options chosen beforehand (weekly paclitaxel, pegylated liposomal doxorubicin, topotecan, letrozole or tamoxifen). After progression, patients in the standard-of-care group could cross over to trametinib. Primary end point investigator-assessed PFS while receiving randomised therapy (ITT).
- Primary endpoint
- PFS
- Arms
- Trametinib (experimental, n = 130): Trametinib 2 mg orally once daily
- Standard of care (control, n = 130): Physician's choice: paclitaxel, pegylated liposomal doxorubicin, topotecan, letrozole or tamoxifen
- People
- Gershenson DM
PFSHR 0.48 (95% CI 0.36–0.64)Δ median PFS+5.8 monthsΔ ORR+20 pointsOSHR 0.76 (95% CI 0.51–1.12)Δ median OS+8.4 months
Show the numbers
| Endpoint | Analysis | Trametinib | Standard of care | Effect |
|---|---|---|---|---|
| PFS | primaryGershenson 2022 | median 13 months (9.9–15.0) | median 7.2 months (5.6–9.9) | HR 0.48 (95% CI 0.36–0.64)P<0.0001Investigator-assessed; 217 PFS events at the primary analysis. |
| ORR | primaryGershenson 2022 | 26% | 6% | P<0.0001Secondary end point. Odds ratio 5.4 (95% CI 2.4-12.2); 34 of 130 vs 8 of 130 patients. |
| OS | exploratoryGershenson 2022 | median 37.6 months | median 29.2 months (23.5–51.6) | HR 0.76 (95% CI 0.51–1.12)P=0.056 (one-sided)Secondary end point at the primary-analysis data cutoff (111 of 260 patients had died). The 95% CI for the trametinib median is 32.0 to not evaluable. The analysis includes the effect of crossover: 88 (68%) of 130 patients in the standard-of-care group crossed over to trametinib. |
| Endpoint | Analysis | Trametinib | Standard of care | Effect |
|---|---|---|---|---|
| PFS | primaryGershenson 2022 | median 13 months (9.9–15.0) | median 7.2 months (5.6–9.9) | HR 0.48 (95% CI 0.36–0.64)P<0.0001Investigator-assessed; 217 PFS events at the primary analysis. |
| ORR | primaryGershenson 2022 | 26% | 6% | P<0.0001Secondary end point. Odds ratio 5.4 (95% CI 2.4-12.2); 34 of 130 vs 8 of 130 patients. |
| OS | exploratoryGershenson 2022 | median 37.6 months | median 29.2 months (23.5–51.6) | HR 0.76 (95% CI 0.51–1.12)P=0.056 (one-sided)Secondary end point at the primary-analysis data cutoff (111 of 260 patients had died). The 95% CI for the trametinib median is 32.0 to not evaluable. The analysis includes the effect of crossover: 88 (68%) of 130 patients in the standard-of-care group crossed over to trametinib. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.48 | 0.36–0.64 |
| OS | 0.76 | 0.51–1.12 |
- Trametinib (experimental)
- Standard of care (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Trametinib | Standard of care |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 8 | 65.3% | 46.3% |
| 16 | 42.6% | 21.4% |
| 24 | 27.8% | 9.9% |
| 33 | 17.2% | 4.2% |
- Trametinib (experimental)
- Standard of care (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Trametinib | Standard of care |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 24 | 64.2% | 56.6% |
| 47 | 42.0% | 32.8% |
| 71 | 27.0% | 18.5% |
| 94 | 17.7% | 10.7% |