Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer.

MedStar author(s):
Citation: New England Journal of Medicine. 372(8):724-34, 2015 Feb 19.PMID: 25693012Institution: Washington Cancer InstituteForm of publication: Journal ArticleMedline article type(s): Clinical Trial, Phase III | Journal Article | Multicenter Study | Randomized Controlled Trial | Research Support, Non-U.S. Gov'tSubject headings: *Antibodies, Monoclonal, Humanized/ad [Administration & Dosage] | *Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use] | *Breast Neoplasms/dt [Drug Therapy] | *Neoplasm Metastasis/dt [Drug Therapy] | *Taxoids/ad [Administration & Dosage] | Adult | Aged | Antibodies, Monoclonal, Humanized/ae [Adverse Effects] | Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects] | Breast Neoplasms/mo [Mortality] | Breast Neoplasms/pa [Pathology] | Double-Blind Method | Female | Humans | Infusions, Intravenous | Middle Aged | Receptor, ErbB-2 | Survival AnalysisYear: 2015Local holdings: Available online from MWHC library: 1993 - present, Available in print through MWHC library: 1980 - presentISSN:
  • 0028-4793
Abstract: BACKGROUND: In patients with metastatic breast cancer that is positive for human epidermal growth factor receptor 2 (HER2), progression-free survival was significantly improved after first-line therapy with pertuzumab, trastuzumab, and docetaxel, as compared with placebo, trastuzumab, and docetaxel. Overall survival was significantly improved with pertuzumab in an interim analysis without the median being reached. We report final prespecified overall survival results with a median follow-up of 50 months.CONCLUSIONS: In patients with HER2-positive metastatic breast cancer, the addition of pertuzumab to trastuzumab and docetaxel, as compared with the addition of placebo, significantly improved the median overall survival to 56.5 months and extended the results of previous analyses showing the efficacy of this drug combination. (Funded by F. Hoffmann-La Roche and Genentech; CLEOPATRA ClinicalTrials.gov number, NCT00567190.).METHODS: We randomly assigned patients with metastatic breast cancer who had not received previous chemotherapy or anti-HER2 therapy for their metastatic disease to receive the pertuzumab combination or the placebo combination. The secondary end points of overall survival, investigator-assessed progression-free survival, independently assessed duration of response, and safety are reported. Sensitivity analyses were adjusted for patients who crossed over from placebo to pertuzumab after the interim analysis.RESULTS: The median overall survival was 56.5 months (95% confidence interval [CI], 49.3 to not reached) in the group receiving the pertuzumab combination, as compared with 40.8 months (95% CI, 35.8 to 48.3) in the group receiving the placebo combination (hazard ratio favoring the pertuzumab group, 0.68; 95% CI, 0.56 to 0.84; P<0.001), a difference of 15.7 months. This analysis was not adjusted for crossover to the pertuzumab group and is therefore conservative. Results of sensitivity analyses after adjustment for crossover were consistent. Median progression-free survival as assessed by investigators improved by 6.3 months in the pertuzumab group (hazard ratio, 0.68; 95% CI, 0.58 to 0.80). Pertuzumab extended the median duration of response by 7.7 months, as independently assessed. Most adverse events occurred during the administration of docetaxel in the two groups, with long-term cardiac safety maintained.All authors: Baselga J, Benyunes MC, Campone M, Ciruelos E, Clark E, CLEOPATRA Study Group, Cortes J, Ferrero JM, Heeson S, Kim SB, Ro J, Ross G, Schneeweiss A, Semiglazov V, Swain SMFiscal year: FY2015Digital Object Identifier: Date added to catalog: 2015-03-18
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Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article 25693012 Available 25693012

Available online from MWHC library: 1993 - present, Available in print through MWHC library: 1980 - present

BACKGROUND: In patients with metastatic breast cancer that is positive for human epidermal growth factor receptor 2 (HER2), progression-free survival was significantly improved after first-line therapy with pertuzumab, trastuzumab, and docetaxel, as compared with placebo, trastuzumab, and docetaxel. Overall survival was significantly improved with pertuzumab in an interim analysis without the median being reached. We report final prespecified overall survival results with a median follow-up of 50 months.

CONCLUSIONS: In patients with HER2-positive metastatic breast cancer, the addition of pertuzumab to trastuzumab and docetaxel, as compared with the addition of placebo, significantly improved the median overall survival to 56.5 months and extended the results of previous analyses showing the efficacy of this drug combination. (Funded by F. Hoffmann-La Roche and Genentech; CLEOPATRA ClinicalTrials.gov number, NCT00567190.).

METHODS: We randomly assigned patients with metastatic breast cancer who had not received previous chemotherapy or anti-HER2 therapy for their metastatic disease to receive the pertuzumab combination or the placebo combination. The secondary end points of overall survival, investigator-assessed progression-free survival, independently assessed duration of response, and safety are reported. Sensitivity analyses were adjusted for patients who crossed over from placebo to pertuzumab after the interim analysis.

RESULTS: The median overall survival was 56.5 months (95% confidence interval [CI], 49.3 to not reached) in the group receiving the pertuzumab combination, as compared with 40.8 months (95% CI, 35.8 to 48.3) in the group receiving the placebo combination (hazard ratio favoring the pertuzumab group, 0.68; 95% CI, 0.56 to 0.84; P<0.001), a difference of 15.7 months. This analysis was not adjusted for crossover to the pertuzumab group and is therefore conservative. Results of sensitivity analyses after adjustment for crossover were consistent. Median progression-free survival as assessed by investigators improved by 6.3 months in the pertuzumab group (hazard ratio, 0.68; 95% CI, 0.58 to 0.80). Pertuzumab extended the median duration of response by 7.7 months, as independently assessed. Most adverse events occurred during the administration of docetaxel in the two groups, with long-term cardiac safety maintained.

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