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Clinical Trial
. 2012 Sep 4;107(6):956-60.
doi: 10.1038/bjc.2012.353. Epub 2012 Aug 14.

Predictive value of HER2 serum levels in patients treated with lapatinib or trastuzumab -- a translational project in the neoadjuvant GeparQuinto trial

I Witzel  1 , S Loibl, G von Minckwitz, H Eidtmann, T Fehm, F Khandan, S Schmatloch, M Hauschild, J Bischoff, P A Fasching, C Mau, C Schem, B Rack, I Meinhold-Heerlein, C Liedtke, T Karn, J Huober, C Zu Eulenburg, Y Issa-Nummer, M Untch, V Müller
Affiliations
Clinical Trial

Predictive value of HER2 serum levels in patients treated with lapatinib or trastuzumab -- a translational project in the neoadjuvant GeparQuinto trial

I Witzel et al. Br J Cancer. .

Abstract

Background: We were able to demonstrate a predictive value of serum HER2 (sHER2) in patients receiving trastuzumab in the neoadjuvant GeparQuattro trial. However, the role of sHER2 in patients receiving neoadjuvant therapy (NT) with lapatinib is still unclear.

Methods: The neoadjuvant GeparQuinto trial compared trastuzumab vs lapatinib in addition to chemotherapy in HER2-positive primary breast cancer patients. The sHER2 levels were measured by enzyme-linked immunosorbant assay in 210 patients, of whom 109 (52%) patients received trastuzumab and 101 (48%) lapatinib at three different time points.

Results: Twenty-two percent of patients had elevated baseline sHER2 levels (>15 ng ml⁻¹). A decrease of sHER2 levels (>20%) in the trastuzumab and lapatinib-treated group during NT was seen in 44% and 24% of the patients, an increase of sHER2 levels (>20%) was seen in 6% and 41% of patients, respectively. Higher pre-chemotherapy sHER2 levels were associated with higher pathological complete remission (pCR) rates in the entire study cohort (OR 1.8, 95% CI 1.02-3.2, P=0.043). A decline of sHER2 levels (>20%) during NT was a predictor for pCR in the lapatinib-treated patient group (OR: 11.7, 95% CI 1.3-110, P=0.031).

Conclusion: Results of this study demonstrate that sHER2 levels change differently during NT depending on the anti-HER2 treatment strategy. Elevated baseline sHER2 levels (>15 ng ml⁻¹) and a decrease of sHER2 levels (>20%) early after therapy initiation are both relevant criteria to predict response to lapatinib-based treatment.

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Conflict of interest statement

Advisory role/remuneration: Gunter von Minckwitz (Roche), Holger Eidtmann (Roche), Tanja Fehm (Roche), Joachim Bischoff (Roche), Peter Fasching (Novartis), Brigitte Rack (Roche, Novartis and GlaxoSmithKline), Jens Huober (Roche and GlaxoSmithKline) and Volkmar Müller (Amgen, Celgene, Sanofi-Aventis, Pierre-Fabre and Roche). Honoraria: Gunter von Minckwitz (Roche) and Peter Fasching (Novartis). Research funding: Gunter von Minckwitz (GlaxoSmithKline and Roche), Tanja Fehm (Roche, Novartis and GlaxoSmithKline), Joachim Bischoff (GlaxoSmithKline), Peter Fasching (Novartis), Jens Huober (GlaxoSmithKline) and Volkmar Müller (Roche). The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Serum collection in the HER2-positive patient cohort in the GeparQuinto trial. Abbreviations: C=cyclophophamide; E=epirubicin; H=trastuzumab; L=lapatinib and T=docetaxel.
Figure 2
Figure 2
Box plot of sHER2 changes after four cycles of chemotherapy in trastuzumab- and lapatinib-treated patients. Patients in the trastuzumab group experienced mainly sHER2 decreases, whereas in the lapatinib group, a significant number of sHER2 increases was observed.
See this image and copyright information in PMC

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