High HER2 expression correlates with response to the combination of lapatinib and trastuzumab Journal Article

Authors: Scaltriti, M.; Nuciforo, P.; Bradbury, I.; Sperinde, J.; Agbor-Tarh, D.; Campbell, C.; Chenna, A.; Winslow, J.; Serra, V.; Parra, J. L.; Prudkin, L.; Jimenez, J.; Aura, C.; Harbeck, N.; Pusztai, L.; Ellis, C.; Eidtmann, H.; Arribas, J.; Cortes, J.; De Azambuja, E.; Piccart, M.; Baselga, J.
Article Title: High HER2 expression correlates with response to the combination of lapatinib and trastuzumab
Abstract: Purpose: Expression of p95HER2 has been associated with resistance to trastuzumab-based therapy in patients with metastatic breast cancer. Conversely, high levels of HER2 have been linked with increased clinical benefit from anti-HER2 therapy. In this work, we aimed to investigate whether the levels of p95HER2 and HER2 can predict response to anti-HER2 therapy in patients with breast cancer. Experimental Design: We measured p95HER2 and HER2 by VeraTag and HERmark, respectively, in primary tumors of patients enrolled in the neoadjuvant phase III study NeoALTTO and correlated these variables with pathologic complete response (pCR) and progression-free survival (PFS) following lapatinib (L), trastuzumab (T), or the combination of both agents (L+T). Results: A positive correlation between p95HER2 and HER2 levels was found in the 274 cases (60%) in which quantification of both markers was possible. High levels of these markers were predictive for pCR, especially in the hormone receptor (HR)-positive subset of patients. High HER2 expression was associated with increased pCR rate upon L+T irrespective of the HR status. To examine whether the levels of either p95HER2 or HER2 could predict for PFS in patients treated with lapatinib, trastuzumab or L+T, we fit to the PFS data in Cox models containing log2 (p95HER2) or log2(HER2). Both variables correlated with longer PFS. Conclusions: Increasing HER2 protein expression correlated with increased benefit of adding lapatinib to trastuzumab. HER2 expression is a stronger predictor of pCR and PFS than p95HER2 for response to lapatinib, trastuzumab and, more significantly, L+T. ©2014 AACR.
Keywords: cancer survival; controlled study; protein expression; major clinical study; overall survival; cancer combination chemotherapy; drug efficacy; monotherapy; cancer adjuvant therapy; outcome assessment; protein function; progression free survival; breast cancer; epidermal growth factor receptor 2; cancer resistance; trastuzumab; lapatinib; predictive value; phase 3 clinical trial (topic); human; article
Journal Title: Clinical Cancer Research
Volume: 21
Issue: 3
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2015-02-01
Start Page: 569
End Page: 576
Language: English
DOI: 10.1158/1078-0432.ccr-14-1824
PUBMED: 25467182
PROVIDER: scopus
Notes: Article -- Export Date: 2 June 2016 -- Source: Scopus
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MSK Authors
  1. Jose T Baselga
    394 Baselga