Pertuzumab Plus Trastuzumab, Docetaxel Extends Survival in HER2-Positive Breast Cancer

CLEOPATRA final results support the addition of pertuzumab to trastuzumab and docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer

medwireNews: Addition of pertuzumab to trastuzumab and docetaxel significantly improves survival compared with the addition of placebo in women with metastatic breast cancer positive for human epidermal growth factor receptor 2, shows the final analysis of a phase III trial.

Median overall survival was 56.5 months for the 402 participants randomly assigned to receive pertuzumab (at a dose of 840 mg on day 1 of cycle 1 followed by 420 mg on day 1 of subsequent cycles) together with trastuzumab and docetaxel in the Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) trial. This compared with 40.8 months for the 406 control patients who were given placebo plus trastuzumab and docetaxel, equating to a difference of 15.7 months.

After a median follow-up of 49.5 months for the pertuzumab treatment arm and 50.6 months for the control arm, the duration of progression-free survival, as evaluated by investigators, was 18.7 and 12.4 months, respectively.

Moreover, the pertuzumab group had a significantly lower likelihood of mortality and of disease progression than the control group, at a hazard ratio (HR) of 0.68 for each endpoint.

Researcher Sandra Swain, from MedStar Washington Hospital Center in the USA, and colleagues explain that after the CLEOPATRA primary endpoint analysis, which showed that pertuzumab significantly prolonged median progression-free survival compared with placebo, patients in the placebo arm had been allowed to crossover to pertuzumab.

They add that this final overall survival analysis was an intention-to-treat one and did not adjust for crossover, which “added to the strength of the findings.”

Indeed, when crossover patients were excluded, the median overall survival was 56.5 months in the pertuzumab group versus 34.7 months in the control group, at a statistically significant HR of 0.55.

“Rates of adverse events remained consistent with those in the primary analysis”, say the authors, with the majority of adverse episodes manifesting during administration of docetaxel and declining when it was discontinued.

Of the 221 adverse events in the patients who crossed over to the pertuzumab group, nine were grade 3 or above, the rest being grade 1 or 2. Moreover, “no new safety signals” were detected in these patients.

Left ventricular dysfunction occurred in 6.6% of patients given pertuzumab and in 8.6% of controls, with one new symptomatic occurrence reported in a pertuzumab-treated patient after 40 months, but none in crossover patients.

These findings led the research team to conclude in The New England Journal of Medicine that “[l]ong-term cardiac safety was maintained.”


Swain SM, Baselga J, Kim S-B, et al. Pertuzumab, Trastuzumab, and Docetaxel in HER2-Positive Metastatic Breast Cancer. N Engl J Med 2015;372: 724–734. doi:10.1056/NEJMoa1413513

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