S41 Targeting HER2 in the adjuvant setting: Dealing with new standards and open questions

Abstract

not received. S41 Targeting HER2 in the adjuvant setting: Dealing with new standards and open questions I.E. Smith1. 1Medicine, The Royal Marsden Hospital and Institute of Cancer Research, London, United Kingdom The HER2 gene is amplified and the receptor overexpressed in around 20% of women with early breast cancer, and this is associated with an adverse prognosis. Trastuzumab (Herceptin), a humanised monoclonal antibody targeted against the external domain of the HER2 receptor, has been shown to have major clinical benefit in all stages of HER2 positive breast cancer including in particular as adjuvant therapy for early disease. The 2007 St Gallen guidelines recommended that trastuzumab should be considered as standard treatment concurrently with or sequentially after chemotherapy in patients with HER2 positive disease which is IHC (immunohistochemistry) 3+ or FISH positive except in those with a primary tumour less than 1 cm and no axillary node involvement. Important unanswered questions remain however. Concurrent or sequential therapy: Three major trials (NSABPB-31; NCCTG N9831 and BCIRG006) have shown significant survival benefit with concurrent trastuzumab given with a taxane chemotherapy following anthracycline treatment. A further major trial (HERA) has shown similar survival benefit with sequential trastuzumab given after standard adjuvant chemotherapy, but another smaller trial of sequential trastuzumab (PACS004) also given after chemotherapy has failed to show benefit. Results from the N9831 trial comparing concurrent with sequential treatment are awaited. Duration of treatment: All the major trials have empirically used one year of adjuvant trastuzumab. The HERA trial is also comparing 2 v.1 year and results are awaited. A much smaller trial (FinHER) has shown similar efficacy gains with a mere 9 weeks of trastuzumab given concurrently with chemotherapy, suggesting that much shorter treatment may be as effective. The role of anthracyclines: Adjuvant trastuzumab after anthracyclines is associated with a small but significant increase in the risk of cardiotoxicity. Results from the BCIRG 006 trial suggest that a non-anthracycline regimen of docetaxel and carboplatin with trastuzumab achieves similar efficacy to anthracycline-containing regimens but without an increase in cardiotoxicity. Standardised measurement of HER2: ASCO and the College of American Pathologists recently convened an expert panel which concluded that around 20% of current HER2 testing may be inaccurate and proposed recommendations for standardised central testing in accredited laboratories with defined proficiency testing requirements. A positive HER2 result should be defined as IHC staining of 3+ (uniform intense membrane staining of greater than 30% of invasive tumour cells) or a fluorescent in situ hybridisation (FISH) result of more than 6 HER2 gene copies per nucleus or a FISH ratio of more than 2.2. ‘Low-risk’ HER2: So called low-risk T1, N0 HER2+ve breast cancers were largely excluded from the major adjuvant trastuzumab trials but data are accumulating that these have significant risk of relapse, even including <1 cm tumours. It is likely that trastuzumab with chemotherapy would also be of benefit in these circumstances; the role of adjuvant trastuzumab alone is plausible here but no direct data are available. New anti-HER2 targeted therapies: These are rapidly becoming available including lapatinib, an oral small molecule dual HER1/HER2tyrosine kinase inhibitor with significant clinical activity in metastatic breast cancer after trastuzumab. Adjuvant single agent lapatinib is being assessed in patients with trastuzumab-naive HER2 positive breast cancer in continuing remission following adjuvant chemotherapy in the TEACH trial. In addition, adjuvant lapatinib and chemotherapy is being compared directly with trastuzumab, or the 2 agents sequentially, or in combination, in the ALTTO trial. S42 Adjuvant therapy of triple negative breast cancer E.A. Perez. Jacksonville, USA Abstract not received.not received. S43 Review of new targeted drugs: Crawling towards the adjuvant