The GeparQuinto study is a phase III study that compared two anti-HER2–targeted agents, lapatinib versus trastuzumab, in combination with chemotherapy for treatment of HER2-positive primary breast cancer. The initial results of this study showed a lower pathologic complete response (pCR; pT0 ypN0) rate when lapatinib was added to standard anthracycline–taxane chemotherapy compared with trastuzumab.
To report the long-term outcomes in patients with HER2-positive tumors from the GeparQuinto trial.
- Female patients with unilateral or bilateral primary invasive breast carcinoma were enrolled in the study
- Breast cancer had to be confirmed histologically by core biopsy.
- HER2 status on tumor biopsy had to be positive by either immunohistochemistry (IHC 3+) or in situ hybridization (ratio> 2.0) by the local pathologist
- Tumor lesions were required to have a palpable size of > 2 cm or size of > 1 cm in maximum diameter and measurable in two-dimensions, preferably by sonography
- In the case of inflammatory disease, the clinical extent of inflammation was used as measurable lesion
- Patients with locally advanced tumors stage cT4 or cT3, hormone receptor-negative tumors (estrogen receptor and progesterone receptor , 10%), or hormone receptor-positive tumors (ER and/or PgR > 10%) with clinically positive axillary nodes (cN+ for cT2 or pNSLN+ for cT1) were eligible
- Patients were randomly assigned to receive either trastuzumab or lapatinib in addition to epirubicin (E) and cyclophosphamide (C), followed by docetaxel (T)
- All patients received four cycles of EC (epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2, day 1, every 3 weeks), followed by four m2, cycles of docetaxel (100mg/day 1, every 3 weeks)
- Trastuzumab 6 mg/kg body weight was administered intravenously every 3 weeks, starting with a loading dose of 8 mg/kg on day 1 of the first EC cycle (ECH-TH) or lapatinib 1,250 mg per day, starting on day 1 of the first cycle of EC until day 21 of the fourth cycle of docetaxel (ECL-TL) concomitantly with all chemotherapy cycles
- Median follow-up was 55 months
- The primary efficacy endpoint for HER2-positive breast cancer of the GeparQuinto study was to compare the pCR rate (ypT0 ypN0) after treatment with trastuzumab or lapatinib, administered concomitantly with neoadjuvant chemotherapy
- The secondary efficacy endpoints (time-to-event endpoints) of the study comparing DFS, distant DFS (DDFS), time to loco-regional relapse (TTLRR), time to CNS metastases (TTCNSM), and OS between treatment arms and in different subgroups
- After a 3-year follow-up,
- DFS, DDFS, and OS did not significantly differ between patients with HER2-positive disease treated with trastuzumab and those who received lapatinib followed by adjuvant trastuzumab
- The subgroup analysis showed that hormone receptor–negative cohort showed that pCR achieved in ECL-TL arm was 70% (22.7%) and 93 (30.3%) of 307 patients in the ECH-TH arm (odds ratio, 0.68; P = .042)
- Overall, patients with pCR (ypT0 ypN0) had statistically significant better DFS, DDFS, and OS compared with patients withresidual disease
- DFS: HR, 0.63; P = .042
- DDFS: HR, 0.55; P = .021
- OS: HR, 0.31; P = .004;
- A benefit only for OS was observed in patients who were treated with trastuzumab and achieved pCR versus no pCR (HR, 0.15; P = .010), whereas no difference was found in patients with pCR versus without pCR in the lapatinib arm
- Subgroup analysis for OS demonstrated a statistically significant interaction between anti-HER2 treatment and hormone receptor status, despite the small number of events observed in each subgroup
- DFS and DDFS remained unchanged in both treatment arms according to hormone receptor status, whereas OS was significantly better in hormone receptor–positive patients who were treated with neoadjuvant lapatinib (HR, 0.32; P = .019), followed by adjuvant trastuzumab
- Neoadjuvant chemotherapy with lapatinib showed a lower pCR rate compared with neoadjuvant chemotherapy with trastuzumab.
- Although the pCR rate after neoadjuvant chemotherapy with lapatinib was significantly lower compared with neoadjuvant chemotherapy with trastuzumab, this did not negatively affect the long-term outcome (DFS, nor on OS), as all lapatinib-treated patients received standard adjuvant trastuzumab for 1 year after surgery.
- Significant improvement in survival was reported in patients with hormone receptor-positive tumors treated with prolonged anti-HER2 treatment-neoadjuvant lapatinib for 6 months, followed by adjuvant trastuzumab for 12 months- compared with anti-HER2 treatment with trastuzumab alone
- The survival benefit observed in this study, particularly in patients with hormone receptor-positive disease who received a sequence of a tyrosine kinase inhibitor with an antibody was in line with findings from the ExteNET study
J Clin Oncol 36:1308-1316.