Carboplatin-paclitaxel with or without trastuzumab in advanced or recurrent HER2/neu-overexpressing uterine serous carcinoma (randomised phase II)
Phase 2N = 61NCT01367002
- Population
- Stage III-IV or recurrent uterine serous carcinoma overexpressing HER2/neu: immunohistochemistry 3+, or 2+ with gene amplification confirmed by FISH (central review); recurrent disease required measurable disease
- Design
- Investigator-initiated multicentre randomised phase 2 trial (11 US academic institutions in the 2020 report), 1:1. Carboplatin AUC 5 and paclitaxel 175 mg/m2 every 21 days for six cycles with or without trastuzumab (8 mg/kg first dose, then 6 mg/kg), followed by maintenance trastuzumab until progression or toxicity. Primary endpoint PFS tested with one-sided log-rank tests (one-sided alpha 0.10); hazard ratios are given with two-sided 90% confidence intervals. 61 patients randomised, 58 evaluable (28 control, 30 trastuzumab).
- Primary endpoint
- PFS
- Arms
- Carboplatin plus paclitaxel (control): Carboplatin AUC 5 and paclitaxel 175 mg/m2 every 21 days for six cycles
- Carboplatin plus paclitaxel plus trastuzumab (experimental): Carboplatin AUC 5 and paclitaxel 175 mg/m2 every 21 days for six cycles with trastuzumab (8 mg/kg then 6 mg/kg), then maintenance trastuzumab
- People
- Fader AN
PFSHR 0.44Δ median PFS+4.6 monthsPFSHR 0.4Δ median PFS+8.6 monthsPFSHR 0.14Δ median PFS+3.2 months
Show the numbers
| Endpoint | Analysis | Carboplatin plus paclitaxel plus trastuzumab | Carboplatin plus paclitaxel | Effect |
|---|---|---|---|---|
| PFS58 evaluable patients (of 61 randomised) | primaryFader 2018 | median 12.6 months | median 8 months | HR 0.44P=0.005 (one-sided)Hazard ratio 0.44 with a 90% confidence interval of 0.26 to 0.76. Forty PFS events occurred among 58 evaluable participants. |
| PFS41 patients with stage III or IV disease undergoing primary treatment | primaryFader 2018 | median 17.9 months | median 9.3 months | HR 0.4P=0.013 (one-sided)Hazard ratio 0.40 with a 90% confidence interval of 0.20 to 0.80. |
| PFS17 patients with recurrent disease | primaryFader 2018 | median 9.2 months | median 6 months | HR 0.14P=0.003 (one-sided)Hazard ratio 0.14 with a 90% confidence interval of 0.04 to 0.53. |
| PFS58 evaluable patients (of 61 randomised) | long term-updatemedian follow-up 25.9 monthsFader 2020 | median 12.9 months | median 8 months | HR 0.46P=0.005 (one-sided)Updated analysis with 43 progressions and 38 deaths. Hazard ratio 0.46 with a 90% confidence interval of 0.28 to 0.76. |
| OS58 evaluable patients (of 61 randomised) | long term-updatemedian follow-up 25.9 monthsFader 2020 | median 29.6 months | median 24.4 months | HR 0.58P=0.046 (one-sided)Overall survival was a secondary endpoint. Hazard ratio 0.58 with a 90% confidence interval of 0.34 to 0.99. |
| OS41 patients with stage III or IV disease undergoing primary treatment | long term-updatemedian follow-up 25.9 monthsFader 2020 | — | — | HR 0.49P=0.041 (one-sided)Hazard ratio 0.49 with a 90% confidence interval of 0.25 to 0.97. Median overall survival was not reached with trastuzumab; the control median is 24.4 months in the abstract and 25.4 months in the full text. |
| Endpoint | Analysis | Carboplatin plus paclitaxel plus trastuzumab | Carboplatin plus paclitaxel | Effect |
|---|---|---|---|---|
| PFS58 evaluable patients (of 61 randomised) | primaryFader 2018 | median 12.6 months | median 8 months | HR 0.44P=0.005 (one-sided)Hazard ratio 0.44 with a 90% confidence interval of 0.26 to 0.76. Forty PFS events occurred among 58 evaluable participants. |
| PFS41 patients with stage III or IV disease undergoing primary treatment | primaryFader 2018 | median 17.9 months | median 9.3 months | HR 0.4P=0.013 (one-sided)Hazard ratio 0.40 with a 90% confidence interval of 0.20 to 0.80. |
| PFS17 patients with recurrent disease | primaryFader 2018 | median 9.2 months | median 6 months | HR 0.14P=0.003 (one-sided)Hazard ratio 0.14 with a 90% confidence interval of 0.04 to 0.53. |
| PFS58 evaluable patients (of 61 randomised) | long term-updatemedian follow-up 25.9 monthsFader 2020 | median 12.9 months | median 8 months | HR 0.46P=0.005 (one-sided)Updated analysis with 43 progressions and 38 deaths. Hazard ratio 0.46 with a 90% confidence interval of 0.28 to 0.76. |
| OS58 evaluable patients (of 61 randomised) | long term-updatemedian follow-up 25.9 monthsFader 2020 | median 29.6 months | median 24.4 months | HR 0.58P=0.046 (one-sided)Overall survival was a secondary endpoint. Hazard ratio 0.58 with a 90% confidence interval of 0.34 to 0.99. |
| OS41 patients with stage III or IV disease undergoing primary treatment | long term-updatemedian follow-up 25.9 monthsFader 2020 | — | — | HR 0.49P=0.041 (one-sided)Hazard ratio 0.49 with a 90% confidence interval of 0.25 to 0.97. Median overall survival was not reached with trastuzumab; the control median is 24.4 months in the abstract and 25.4 months in the full text. |
- Carboplatin plus paclitaxel plus trastuzumab (experimental)
- Carboplatin plus paclitaxel (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Carboplatin plus paclitaxel plus trastuzumab | Carboplatin plus paclitaxel |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 8 | 64.4% | 50.0% |
| 16 | 41.5% | 25.0% |
| 24 | 26.7% | 12.5% |
| 32 | 17.2% | 6.3% |
- Carboplatin plus paclitaxel plus trastuzumab (experimental)
- Carboplatin plus paclitaxel (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Carboplatin plus paclitaxel plus trastuzumab | Carboplatin plus paclitaxel |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 11 | 65.3% | 44.0% |
| 22 | 42.7% | 19.4% |
| 34 | 26.8% | 7.9% |
| 45 | 17.5% | 3.5% |
Appears in
Sources
Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, et al. Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu. J Clin Oncol. 2018;36(20):2044-2051.
Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, et al. Randomized Phase II Trial of Carboplatin-Paclitaxel Compared with Carboplatin-Paclitaxel-Trastuzumab in Advanced (Stage III-IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis. Clin Cancer Res. 2020;26(15):3928-3935.