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Expert Describes Discouraging Neoadjuvant Data in HER2+ Breast Cancer

Gina Columbus @ginacolumbusonc
Published: Thursday, Dec 10, 2015

Gunter von Minckwitz, MD, PhD

Gunter von Minckwitz, MD, PhD

Neoadjuvant treatment regimens in HER2-positive breast cancer are being investigated, but early results presented at the 2015 San Antonio Breast Cancer Symposium demonstrate that the therapies may not elicit a significant benefit in patients.

An early survival analysis of the phase II GeparSixto study, which examined the addition of carboplatin to neoadjuvant therapy for patients with triple-negative breast cancer (TNBC) and those with HER2-positive breast cancer, showed a survival benefit in TNBC, though the same could not be said for HER2-positive disease, explained Gunter von Minckwitz, MD.

In this study, HER2-positive patients (n = 273) received concurrently trastuzumab 6(8)mg/kg every 3 weeks and lapatinib at 750 mg daily. All patients were randomized 1:1 to receive concurrently carboplatin AUC 1.5-2.0 q1w versus no carboplatin, stratified by subtype (HER2-positive vs TNBC).

Secondly, an analysis of BRCA mutations, therapy response, and prognosis of three subgroups of patients—including HER2-positive, HER2-negative, and TNBC—enrolled in the GeparQuinto study, will be reported.

HER2-positive patients who received lapatinib instead of trastuzumab experienced significantly lower pathological complete response (pCR) rates. Moreover, survival data do not show a significant inferior survival for the laparinib patients, explained von Minckwitz.

Also being reported during the meeting is a 3-year analysis of results from the phase III randomized, placebo-controlled, double-blind ExteNET study, which examined neratinib after trastuzumab-based adjuvant therapy in patients with early-stage HER2-positive breast cancer. In the 2-year analysis, the disease-free survival rate was 93.9% in the neratinib arm versus 91.6% with placebo, representing a 33% reduction in the risk of recurrence (HR, 0.67; 95% CI, 0.50-0.91; P = .009). However, 95.4% of patients treated with neratinib experienced all-grade diarrhea, including 39.9% experiencing grade 3/4.

In an interview with OncLive during the symposium in San Antonio, Texas, von Minckwitz, professor and president of German Breast Group research GmbH, discussed these less-than-encouraging results and what next steps lie ahead in neoadjuvant therapy regimens for HER2-positive breast cancer.

OncLive: What were the goals of the GeparSixto study?

von Minckwitz: The goal of the GeparSixto study was to explore how far the addition of carboplatin to standard or a full chemotherapy-targeted backbone treatment can improve pCR in either HER2-positive breast cancer or TNBC. Patients with HER2-positive disease received weekly paclitaxel and non–pegylated-liposomal doxorubicin, and were concurrently scheduled to receive trastuzumab and pertuzumab. Patients with TNBC received bevacizumab as a targeted agent. In the experimental arm, carboplatin was added. In the weekly schedule, we started it at a dose of AUC 2, but then reduced it after half of the patients were recruited to AUC 1.5. This appeared to be better tolerated by patients.

What were the significant findings of the study?

Two years ago, we reported that the pCR rate of this study was significantly higher when carboplatin was added. We saw that this effect was mainly in patients with TNBC. There was no effect, even in numerically, even somewhat lower pCR rate, in HER2-positive patients.

Now, at this meeting, we are presenting survival data of this study. Again, we see that carboplatin significantly improves disease-free survival in TNBC patients but not in patients with HER2-positive disease. The hazard ratio in TNBC patients is 0.56, which demonstrated a very extensive beneficial effect of carboplatin in this population.

Is there an understanding of why the addition of carboplatin was not found to be effective in patients with HER2-positive disease?

We can only hypothesize. There is only one other study looking into that. Here, carboplatin was not given in addition; it was a replacement of anthracycline and cyclophosphamide, so it is a different situation.

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