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MADRID -- Women with metastatic HER2-positive breast cancer had a median overall survival (OS) approaching 5 years when treated with a combination of two anti-HER2 antibodies, final results of a randomized trial showed.

Patients who received trastuzumab (Herceptin) plus pertuzumab (Perjeta) had a median survival of 56.5 months compared with 40.8 months for patients treated with trastuzumab alone. No new safety issues emerged from the long-term follow-up in the trial, including cardiac safety, according to a presentation here at the European Society of Medical Oncology meeting.

"The 56.5-month median overall survival is unprecedented in this indication, as is the 15.7-month improvement in median survival," said Sandra Swain, MD, of in Washington, DC. "The outcome confirms the pertuzumab regimen as first-line standard of care for patients with HER2-positive metastatic breast cancer.

"This is the kind of survival improvement for which we have worked, and this data will be incredibly meaningful to patients and their families."

ESMO spokesperson , of in Barcelona, agreed with Swain that the pertuzumab-trastuzumab combination will change practice with respect to the management of metastatic HER2-positive breast cancer.

"We should consider this combination as the standard of care for our patients," Cortes said in a statement. "I can see no reason to justify the use of trastuzumab without pertuzumab."

Swain reported final results from the CLEOPATRA (CLinical Evaluation Of Pertuzumab And TRAstuzumab) trial involving patients with metastatic HER2-positive breast cancer. From the initial report, the combination of the two anti-HER2 agents demonstrated superiority over trastuzumab alone. At the first interim analysis, the trial met the primary endpoint of progression-free survival and also showed a trend toward better OS.

As follow-up in the trial progressed, the survival difference achieved statistical significance and continued to increase. A second interim report in 2012 showed a significant difference in OS in the pertuzumab group, but the median OS had yet to be reached in the pertuzumab arm.

CLEOPATRA investigators in North America, Europe, and Asia randomized 808 patients to first-line treatment with trastuzumab and docetaxel, plus either placebo or pertuzumab. Swain reported data from a median follow-up of 50 months.

The 15.7-month difference in OS translated into a 32% reduction in the survival hazard for the pertuzumab arm (HR 0.68, P=0.0002).

Because pertuzumab and trastuzumab carry a potential risk of cardiotoxicity, investigators monitored cardiac function throughout the trial. The final analysis showed a 1.8% incidence of symptomatic left ventricular dysfunction in the placebo arm and 1.5% in the pertuzumab arm. The proportion of patients who had declines in left ventricular ejection fraction <50% and ≥10% was 7.4% with trastuzumab alone and 6.1% with trastuzumab plus pertuzumab.

"One new symptomatic left ventricular dysfunction event in the pertuzumab group occurred after 40 months of follow-up, and it resolved," Swain said. "Overall, 88% of left ventricular declines reversed in pertuzumab-treated patients."

The CLEOPATRA results were particularly impressive in light of the survival in control group, which exceeded expectations, said , of the Mayo Clinic in Jacksonville, Fla.

"Based on the CLEOPATRA data, we solidified the notion that, for patients eligible to receive first-line treatment, for HER2-positive metastatic breast cancer, patients should receive a triplet of chemotherapy in combination with trastuzumab and pertuzumab," Perez told 乌鸦传媒視頻.