According to the final analysis of CLEOPATRA, first-line treatment with pertuzumab plus trastuzumab and docetaxel significantly improves overall survival for patients with HER2-positive metastatic breast cancer. As such, dual HER2 blockade plus chemotherapy should be the standard of care in this setting, researchers say.

Nearly 3 years after initial data from the phase III CLEOPATRA trial were reported, pertuzumab (Perjeta; Genentech) combined with trastuzumab (Herceptin; Genentech) and docetaxel is now widely considered a therapeutic success against metastatic HER2-positive breast cancer. According to the third and final analysis, the median overall survival (OS) for patients on this dual HER2-blockade regimen was 56.5 months, compared with 40.8 months for those randomized to receive a placebo with trastuzumab and docetaxel.

Sandra Swain, MD, medical director of the Washington Cancer Institute in Washington, DC, and CLEOPATRA's lead author, presented the latest data on September 28 at the 2014 European Society for Medical Oncology Congress in Madrid, Spain. The median OS for patients in the control group was already “very good,” she said, but the 16-month increase in survival achieved with the addition of pertuzumab was “phenomenal” and “unprecedented in the first-line setting.”

CLEOPATRA included 808 patients from 25 countries, and its initial results led to FDA approval of pertuzumab in 2012 for use with trastuzumab and docetaxel against HER2-positive breast cancer. That same year, patients in the study's control arm were offered the opportunity to cross over to the experimental arm, and 48 opted to do so. Because these patients continued to be analyzed as part of the control group, the results reported at ESMO represent “a very conservative final analysis,” Swain said.

Consistent with previous follow-ups, the updated analysis of median progression-free survival indicated an improvement of 6.3 months with pertuzumab. The drug's known side effects, including dry skin and diarrhea, remained unchanged, with no new safety concerns or significant cardiac toxicity.

For Swain, these data confirm that dual HER2 blockade, along with chemotherapy, should be the standard of care for metastatic HER2-positive breast cancer. Luca Gianni, MD, medical oncology director at the Instituto Nazionale dei Tumori in Milan, Italy, agreed, adding that future research should examine features of HER2-positive breast cancer that may drive resistance, including mutations in PIK3CA.

©2014 American Association for Cancer Research.
2014