33rd
Annual San Antonio Breast Cancer Symposium
When added to neoadjuvant therapy, trastuzumab yielded nearly 10% higher
response rates than lapatinib in women with HER2-positive metastatic breast
cancer, according to findings presented here.
Lapatinib previously has demonstrated efficacy of cytotoxic and
endocrine treatment in HER2-positive metastatic breast cancer patients. The
addition of trastuzumab to neoadjuvant therapy yielded improved pathological CR
rates in prior studies.
The researchers in the GeparQuinto study aimed to determine whether the
addition of lapatinib rather than trastuzumab to anthracycline-taxane-based
neoadjuvant chemotherapy would lead to improved pathological CR rates. The
researchers defined pathological CR as no invasive or non-invasive tumor
residuals in the breast and nodes.
Protocols
Untch reviewed eligibility criteria for patients:
- cT3/4a-d;
- estrogen or progesterone receptor-negative; or
- estrogen/progesterone-positive tumors with clinically N+ (for cT2) or
pNSLN+ (for cT1) disease; and
- no increased cardiac risks.
Patients were enrolled between May 2007 and June 2010. There were 299
patients in the trastuzumab arm and 298 patients in the lapatinib arm.
All patients received four cycles of epirubicin/cyclophosphamide at
90/600 mg/m2 every 3 weeks followed by four cycles of docetaxel at
100 mg/m2. Patients were randomly assigned either trastuzumab at a
loading dose of 8 mg/kg then 6 mg/kg every 3 weeks or lapatinib 1,000-1,250
mg/d throughout all cycles to be given with the baseline regimen.
Treatment was given for 6 months before surgery. Patients in the
trastuzumab arm continued therapy for an additional 6 months; those in the
lapatinib arm were treated for another 12 months.
Patients in the trastuzumab/lapatinib groups had a median tumor size of
40/40 mm clinically and 28/29 mm sonographically; 4.7%/4/3% had T4a-c;
14.8%/14.2 had T4d; 2.9%/1.8% bilateral; 17.0%/17.7% multifocal; 9.0%/12.1% had
multicentric disease; 96.7%/97.9% non-lobular; 45.6%/48.9% grade 3; 70.0%/67.7%
node-positive; and 56.5%/56.0% estrogen and progesterone-negative disease,
according Untch.
“This is a mix of patients with early breast cancer and
locally-advanced
breast cancer,” he said.
Trastuzumab performed
The pathological CR rate in the trastuzumab arm was 31.3%, compared with
21.7% in the lapatinib arm (P≤.05), based on central pathology report
review.
“These rates are based on the most stringent criteria,” Untch
said. He noted that this value is significant.
“To be in line with other presentations and published data, we
included two other definitions of pathologic complete response rate,”
Untch said.
He noted that when defined as no invasive residual in the breast and
nodes, the response rates were 45% in the trastuzumab group and 29.9% in the
lapatinib group (P≤.05). When defined as no invasive residuals in the
breast, the rates were 50.4% in the trastuzumab group and 35.2% in the
lapatinib group (P≤.05).
“In both of these subgroup analyses, it is notable that the results
are statistically significant,” Untch said.
Untch added that the results confirm previous findings on trastuzumab
efficacy.
Ten percent of patients in the trastuzumab arm and 16% of patients in
the lapatinib arm discontinued all treatment. The discontinuation rates for the
targeted drugs were 3.1% for trastuzumab and 7.0% for lapatinib.
“Lapatinib had a significantly lower pathologic complete response
rate, and 10% more discontinuations overall,” he said. “Compliance of
lapatinib was also lower than with trastuzumab.”
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