Pertuzumab, Trastuzumab, and Docetaxel in HER2-Positive Metastatic Breast Cancer

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. 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. CONCLUSIONS In patients with HER2-positive metastatic breast cancer, the addition of per tuzumab 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.)

Assessing HER2 testing quality in breast cancer: variables that influence HER2 positivity rate from a large, multicenter, observational study in Germany

“…[2][3][4] HER2 is a prognostic biomarker predictive for the response to HER2-targeted therapies including the recombinant monoclonal antibodies trastuzumab and pertuzumab, and the antibody-drug conjugate ado-trastuzumab emtansine, all of which specifically target HER2 and are effective treatments for HER2-positive breast cancer. [5][6][7][8][9][10][11][12][13] Pertuzumab, in combination with trastuzumab plus docetaxel, for example, demonstrated statistically significant and clinically relevant improvements in progression-free and overall survival as first-line treatment of patients with HER2-positive metastatic breast cancer (compared with placebo, trastuzumab, and docetaxel). 9,13 A prerequisite for receiving HER2-targeted therapy is the identification of HER2-overexpression either in the primary tumor or in metastatic lesions.…”

Trastuzumab in Female Breast Cancer Patients With Reduced Left Ventricular Ejection Fraction

“…The introduction of HER2‐directed therapy has revolutionized the treatment and survival expectations for women with HER2+ breast cancer,25 even for those with metastatic disease 26. Our data suggest that such lifesaving therapy should not be withheld out of concern of a higher cardiotoxicity risk in most women with a reduced cardiac function.…”

Improved decision making for prioritizing tumor targeting antibodies in human xenografts: Utility of fluorescence imaging to verify tumor target expression, antibody binding and optimization of dosage and application schedule

“…Both molecules are excellently suited for this application because binding characteristics were already described in the literature 44 and their combination therapy is successfully used in clinical practice. [45][46][47] The in vivo imaging results demonstrated that fluorescentlabeled trastuzumab and pertuzumab showed identical penetration and accumulation behavior in Calu-3 tumor xenograft after 24 h of incubation (Fig. 4D, H, L, M).…”