Overall survival benefit with pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer in CLEOPATRA, a randomised Phase 3 study
By S. Swain, Sung-Bae Kim, J. Cortés, J. Ro, V. Semiglazov, M. Campone, E. Ciruelos, J. Ferrero, A. Schneeweiss, A. Knott and 4 more. The Lancet Oncology, 2013
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Summary Background Primary results from the randomised, double-blind phase 3 study CLEOPATRA demonstrated significantly improved median progression-free survival (PFS) with pertuzumab plus trastuzumab plus docetaxel versus placebo plus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-positive first-line metastatic breast cancer (MBC). Overall survival (OS) data at the primary analysis showed a strong trend in favour of the pertuzumab arm but did not reach statistical significance. Here we report confirmatory OS results after one additional year of follow-up. Methods Patients were randomly assigned to study treatment. OS and investigator-assessed PFS were analysed using the Kaplan-Meier approach and log-rank tests stratified by geographic region and prior treatment status. This trial is registered with ClinicalTrials.gov, NCT00567190. Findings In the intent-to-treat population (808 patients), 267 deaths had occurred at data cut-off (placebo arm: 154 of 406 [37·9%], pertuzumab arm: 113 of 402 [28·1%]). Treatment with pertuzumab plus trastuzumab plus docetaxel resulted in a 34% reduction in the risk of death during the course of the study (HR=0·66; 95% CI 0·52–0·84; p=0·0008). Median OS was 37·6 months in the placebo arm and was not yet reached in the pertuzumab arm. A descriptive follow-up analysis of investigator-assessed PFS showed a median PFS of 12·4 and 18·7 months in the placebo versus pertuzumab arm (HR=0·69; 95% CI 0·58–0·81). No new safety concerns were identified with one additional year of follow-up. Adverse events were similar to those reported at the primary analysis with respect to incidence, severity, and specificity. Interpretation This OS analysis demonstrated statistically significant and clinically meaningful survival benefit with pertuzumab plus trastuzumab plus docetaxel in patients with HER2-positive MBC. Updated analyses of investigator-assessed PFS and safety were consistent with the results from the primary analysis. Funding F. Hoffmann-La Roche/Genentech
Subfields: Cancer Research, Oncology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/763adc22bcf207ce25b40e52f3c78e1246129cd7
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Citations in the corpus
- 4th ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4)† (2018, methodology): “With the publication of the CLEOPATRA trial [45] results showing a substantial OS benefit, a non-data-driven protocol amendment was made to change the primary endpoint to PFS, in agreement with the regulatory authorities.”
- A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). (2015, neutral): “84) No improvement 4 [91-94]”
- ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2) (2014, result): “The CLEOPATRA trial [96,97]; showed superior results, in terms of PFS (18.”