CLEOPATRA Affirms Principle of Dual HER2 Blockade in HER2+ Metastatic Breast Cancer

Dual HER2 blockade with trastuzumab plus pertuzumab combined with docetaxel chemo - therapy significantly extended progression- free survival (PFS) by about 6 months compared to trastuzumab plus docetaxel plus placebo in patients with metastatic HER2-positive breast cancer, according to results from the CLEOPATRA trial presented at the CTRCAACR San Antonio Breast Cancer Symposium.

“These findings represent a significant advance in the treatment of advanced breast cancer. The results may be practice changing,” said senior author Jose Baselga, MD, PhD, Professor at Harvard Medical School and Associate Director of Massachusetts General Hospital in Boston.

These results affirm the concept of dual HER2 blockade in HER2-positive metastatic breast cancer. Pertuzumab and trastuzumab have distinct mechanisms of action and bind at different sites. “The 2 antibodies are extremely complementary and synergistic in preliminary studies,” he said.

CLEOPATRA was a randomized registration phase 3 study for pertuzumab. The study randomized 808 patients in a 1:1 ratio to trastuzumab/docetaxel chemotherapy with pertuzumab or placebo. Docetaxel was given every 3 weeks for 6 cycles in both arms, and investigators could decide whether to continue it on an individual basis. Both monoclonal antibodies were given every 3 weeks until evidence of disease progression. Patients had no prior therapy for metastatic disease, except 1 line of prior hormone therapy was allowed. Prior chemotherapy was allowed if 1 year had passed. More than three-quarters of patients had visceral metastases; the remainder had metastases confined to the bone.

By independent review, median PFS was 12.4 months in the control arm versus 18.5 months in the experimental arm, which was highly statistically significant (P <.0001).

All prespecified subgroups benefitted from dual HER2 blockade, with the exception of patients with nonvisceral metastasis. A strong trend toward improved overall survival was observed for the experimental arm, but this was an interim analysis, and the data need to be more mature for meaningful survival results, Baselga said.

Treatment was safe and tolerable, with no cardiac toxicity observed. Only minimal side effects were seen with the addition of pertuzumab, including grades 1 and 2 diarrhea and neutropenia.

“This represents an advance in treatment of HER2-positive breast cancer,” said Lisa Carey, MD, University of North Carolina at Chapel Hill, North Carolina, who moderated the press conference where CLEOPATRA was discussed. “The challenge now is to find biomarkers to identify which patients will derive benefit from dual HER2 blockade,” she said.