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Pertuzumab, trastuzumab gain further credibility as adjuvant therapies
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33rd Annual San Antonio Breast Cancer Symposium
SAN ANTONIO — Addition of trastuzumab and pertuzumab to docetaxel was associated with a pathological complete response rate of more than 45% in women with metastatic HER2-positive breast cancer, according to results presented here.
Luca Gianni, MD, head of the Laboratory of Clinical Pharmacology in the Division of Medical Oncology at the Istituto Nazionale dei Tumori in Milan, Italy, said that pertuzumab binds to HER2 and has a complementary mechanism of action with trastuzumab.
The current study is a phase 2 randomized trial of preoperative systemic therapy comparing four cycles of IV therapy before surgery every 3 weeks in the following regimens:
- docetaxel (75 mg/m2 with escalation to 100 mg/m2 if the starting dose was well tolerated)/trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance dose);
- docetaxel/trastuzumab plus pertuzumab (840 mg loading, 420 mg maintenance);
- trastuzumab and pertuzumab; and
- docetaxel and pertuzumab.
Eligible patients had centrally-confirmed HER2-positive, stage 2 or 3 — including locally-advanced — breast cancer (defined as IHC 3+ or FISH positive).
Before surgery, there were 107 patients in the docetaxel/trastuzumab, docetaxel/trastuzumab plus pertuzumab and trastuzumab/pertuzumab groups and 96 patients in the docetaxel/pertuzumab group.
After surgery, all patients received the trastuzumab regimen to 1 year and three cycles of fluoroucil, epirubicin and cyclophosphamide (FEC).
The primary outcome measure was the rate of pathological CR in the breast, according to the study.
Biomarker analyses were conducted on tissue samples taken at baseline and at surgery after four cycles of neoadjuvant therapy.
Intention-to-treat analysis results indicated that the pathological CR rate was significantly higher for docetaxel/trastuzumab plus pertuzumab than it was for docetaxel/trastuzumab (P=.014). In turn, the docetaxel/trastuzumab regimen had significantly higher pathological CR rates than trastuzumab/pertuzumab (P=.031).
“There was substantial antitumor activity and a favorable therapeutic ratio associated with the docetaxel, trastuzumab and pertuzumab regimen,” Gianni said. He noted a pathological CR rate of 45.8% in the three-drug combination group.
One patient in the docetaxel/trastuzumab group had clinical disease progression, as did two patients in the trastuzumab/pertuzumab group.
All arms containing docetaxel had good feasibility, according to Gianni.
Adverse event data indicated that grade 3 or higher events occurred in less than 7% of patients receiving trastuzumab/pertuzumab, compared with rates of more than 50% in patients receiving docetaxel.
“The tolerability of all combinations was good,” Gianni said.
“The addition of pertuzumab and trastuzumab has at least additive efficacy,” Gianni added. “This should be further explored in phase 3 trials, and continued use as adjuvant therapy is justified.”
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