CLEOPATRA
A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Pertuzumab + Trastuzumab + Docetaxel vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-Positive Metastatic Breast Cancer
Phase 3N = 808NCT00567190
- Population
- HER2-positive metastatic breast cancer with no previous chemotherapy or biological treatment for metastatic disease
- Design
- Double-blind, randomised, placebo-controlled phase 3 trial (204 centres in 25 countries, 1:1 randomisation stratified by region and prior adjuvant or neoadjuvant chemotherapy). Pertuzumab or placebo and trastuzumab were given every three weeks until progression; docetaxel for six cycles or longer at the investigators' discretion.
- Primary endpoint
- PFS
- Arms
- Placebo + trastuzumab + docetaxel (control, n = 406): Placebo plus trastuzumab plus docetaxel
- Pertuzumab + trastuzumab + docetaxel (experimental, n = 402): Pertuzumab plus trastuzumab plus docetaxel
- People
- Baselga J
PFSHR 0.62 (95% CI 0.51–0.75)Δ median PFS+6.1 monthsPFSHR 0.68 (95% CI 0.58–0.80)OSHR 0.68 (95% CI 0.56–0.84)Δ median OS+15.7 monthsOSHR 0.69 (95% CI 0.58–0.82)
Show the numbers
| Endpoint | Analysis | Pertuzumab + trastuzumab + docetaxel | Placebo + trastuzumab + docetaxel | Effect |
|---|---|---|---|---|
| PFSIndependently assessed progression-free survival (primary endpoint) | primaryBaselga 2012 | median 18.5 months | median 12.4 months | HR 0.62 (95% CI 0.51–0.75)P<0.001 |
| PFSAll randomised patients (analysis population not stated in the abstract)Investigator-assessed progression-free survival | long term-updatemedian follow-up 50 monthsSwain 2015 | — | — | HR 0.68 (95% CI 0.58–0.80)Reported in the final prespecified overall survival analysis paper; median progression-free survival as assessed by investigators improved by 6.3 months in the pertuzumab group (medians not given in the abstract). |
| OSAll randomised patients (analysis population not stated in the abstract) | finalmedian follow-up 50 monthsSwain 2015 | median 56.5 months | median 40.8 months (35.8–48.3) | HR 0.68 (95% CI 0.56–0.84)P<0.001Final prespecified overall survival analysis; difference of 15.7 months. The 95% confidence interval for the pertuzumab median is 49.3 to not reached (upper bound not representable). Not adjusted for crossover from placebo to pertuzumab; the authors call this conservative. |
| OS | long term-updateSwain 2020 | median 57.1 months (50–72); 37% at 8 y (31–42%) | median 40.8 months (36–48); 23% at 8 y (19–28%) | HR 0.69 (95% CI 0.58–0.82)End-of-study descriptive analysis (clinical cutoff 23 November 2018); median follow-up 99.9 months in the pertuzumab group and 98.7 months in the placebo group. Eight-year landmark overall survival shown. Crossover patients analysed in the placebo group. |
| Endpoint | Analysis | Pertuzumab + trastuzumab + docetaxel | Placebo + trastuzumab + docetaxel | Effect |
|---|---|---|---|---|
| PFSIndependently assessed progression-free survival (primary endpoint) | primaryBaselga 2012 | median 18.5 months | median 12.4 months | HR 0.62 (95% CI 0.51–0.75)P<0.001 |
| PFSAll randomised patients (analysis population not stated in the abstract)Investigator-assessed progression-free survival | long term-updatemedian follow-up 50 monthsSwain 2015 | — | — | HR 0.68 (95% CI 0.58–0.80)Reported in the final prespecified overall survival analysis paper; median progression-free survival as assessed by investigators improved by 6.3 months in the pertuzumab group (medians not given in the abstract). |
| OSAll randomised patients (analysis population not stated in the abstract) | finalmedian follow-up 50 monthsSwain 2015 | median 56.5 months | median 40.8 months (35.8–48.3) | HR 0.68 (95% CI 0.56–0.84)P<0.001Final prespecified overall survival analysis; difference of 15.7 months. The 95% confidence interval for the pertuzumab median is 49.3 to not reached (upper bound not representable). Not adjusted for crossover from placebo to pertuzumab; the authors call this conservative. |
| OS | long term-updateSwain 2020 | median 57.1 months (50–72); 37% at 8 y (31–42%) | median 40.8 months (36–48); 23% at 8 y (19–28%) | HR 0.69 (95% CI 0.58–0.82)End-of-study descriptive analysis (clinical cutoff 23 November 2018); median follow-up 99.9 months in the pertuzumab group and 98.7 months in the placebo group. Eight-year landmark overall survival shown. Crossover patients analysed in the placebo group. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.62 | 0.51–0.75 |
| PFS | 0.68 | 0.58–0.8 |
| OS | 0.68 | 0.56–0.84 |
| OS | 0.69 | 0.58–0.82 |
- Placebo + trastuzumab + docetaxel (control)
- Pertuzumab + trastuzumab + docetaxel (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Placebo + trastuzumab + docetaxel | Pertuzumab + trastuzumab + docetaxel |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 12 | 51.1% | 63.8% |
| 23 | 27.6% | 42.2% |
| 35 | 14.1% | 26.9% |
| 46 | 7.6% | 17.8% |
- Placebo + trastuzumab + docetaxel (control)
- Pertuzumab + trastuzumab + docetaxel (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Placebo + trastuzumab + docetaxel | Pertuzumab + trastuzumab + docetaxel |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 35 | 55.2% | 65.1% |
| 71 | 29.9% | 41.9% |
| 106 | 16.5% | 27.2% |
| 141 | 9.1% | 17.7% |
Appears in
Sources
Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366(2):109-19.
Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372(8):724-34.
Swain SM, Miles D, Kim SB, Im YH, Im SA, Semiglazov V, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(4):519-530.