CLEOPATRA: Record-Breaking Survival in HER2 Metastatic Breast Cancer by Adding Pertuzumab
Madrid, Spain—Final results from the CLEOPATRA (Clinical Evaluation of Pertuzumab and Trastuzumab) trial show that dual HER2 blockade with the combination of pertuzumab and trastuzumab plus chemotherapy extended overall survival (OS) by almost 16 months compared with trastuzumab plus chemotherapy alone in patients with HER2-positive metastatic breast cancer. This should become the new standard of care for patients with metastatic HER2 disease, according to the study investigators, who presented their results at the 2014 European Society for Medical Oncology (ESMO) Congress.
“The final results of CLEOPATRA show that the addition of pertuzumab to standard therapy [trastuzumab plus docetaxel] significantly improved overall survival by 15.7 months. I am so pleased to present these results. The 56.5-month median overall survival is unprecedented for this indication,” stated lead investigator Sandra M. Swain, MD, Medical Director, Washington Cancer Institute, MedStar Washington Hospital Center, Washington, DC, and former president of the American Society of Clinical Oncology.
These findings confirm interim results reported 2 years ago, Dr Swain said. “Two monoclonal antibodies that bind at different sites of the HER2 receptor, used together, not sequentially, extended survival,” she told listeners at the meeting.
CLEOPATRA enrolled 808 patients with centrally confirmed HER2-positive metastatic breast cancer from 204 centers in 25 countries. Patients were randomized to treatment with placebo plus trastuzumab and docetaxel versus pertuzumab plus trastuzumab and docetaxel. Docetaxel was given for at least 6 cycles (median, 8 cycles), and both monoclonal antibodies were given until disease progression.
The final OS analysis was presented after a median follow-up of 50 months. “This is 20 months longer than the last interim analysis,” Dr Swain noted.
Median OS was 56.5 months for the dual HER2 blockade arm versus 40.8 months for patients who received trastuzumab plus docetaxel, representing a significant 32% increase in the risk of survival (P = .002).
“This change of 15.7 months has changed things for HER2-positive patients. I have never seen a survival benefit of this magnitude in metastatic HER2-positive breast cancer,” Dr Swain said.
The OS improvement was in the context of a 6.3-month improvement in progression-free survival (PFS) reported in the updated final analysis. “PFS was significantly improved in the interim analyses [6.1 improvement] and in the final analysis. This shows that in this blinded study, PFS was a good surrogate for OS,” she continued.
There was concern that the combination of 2 monoclonal antibodies would lead to additional toxicities. In this study, rash, mucositis, and diarrhea were increased in the pertuzumab-containing arm compared with trastuzumab plus docetaxel.
There was no increase in cardiac toxicities with dual HER2 blockade. Asymptomatic declines in left-ventricular (LV) ejection fraction were actually less with the combination (6.1% vs 7.4%), and symptomatic LV dysfunction was reported in 1.5% and 1.8% of patients, respectively.
These decreases in heart function were reversible in 88% of patients in the combination arm, Dr Swain said.
A New Standard of Care
“This study confirms the pertuzumab/trastuzumab regimen as standard of care for first-line therapy in patients with HER2-positive metastatic breast cancer,” Dr Swain said.
“The median overall survival data presented by Dr Sandra Swain here, at ESMO 2014, with pertuzumab and trastuzumab-based therapy in patients with HER2-positive metastatic breast cancer are remarkable. This is one of the biggest steps toward making this disease a chronic condition in the near future,” said Javier Cortés, MD, PhD, Head, Breast Cancer Program, Vall d’Hebron University Hospital, Barcelona, Spain, and coinvestigator of CLEOPATRA.
“We should consider this combination as the standard of care for our patients. I can see no reason to justify the use of trastuzumab without pertuzumab,” Dr Cortés added.