Combination Treatment Causes Some HER2 Breast Cancers To Regress Quickly Interview with:

Professor Nigel Bundred MD, FRCS Professor of Surgical Oncology Institute of Cancer Sciences University Hospital of South Manchester

Dr. Nigel Bundred

Professor Nigel Bundred MD, FRCS
Professor of Surgical Oncology
Institute of Cancer Sciences
University Hospital of South Manchester What is the background for this study?

Dr. Bundred: HER-2 is a cancer-causing gene which is expressed in some cells by having more copies of the gene and predicts for early relapse and metastasis from the tumour. Despite this, even in the absence of anything other than local treatment, some 50% of patients still survive for five years without relapse.

Herceptin was discovered and licensed for use in 2006 because it improved survival when given with chemotherapy after surgery, from 66% at five years to 90% at five years.

The use of Herceptin and chemotherapy before surgery to shrink the tumour indicates that around 30% of patients have a complete pathological response with this treatment.

Combination of dual anti-HER-2 therapies and  Neoadjuvant chemotherapy given for six months before surgery has been shown to increase pCR rate to 50% and a single study utilising the combination of pertuzumab and trastuzumab (two anti-HER-2 monoclonal antibodies) given for four months revealed a 16.8% pCR rate. What are the main findings?

Dr. Bundred: This study, EPHOS-B, identified 10% of patients with a pCR within 11 days of treatment (and 16% where small amounts of invasive cancer were left)and potentially this strategy could be used to identify who could avoid chemotherapy, although this would require further trials. It will also identify responders and could allow individualisation of HER-2 therapy so that non-responders might switch treatment to another anti-HER-2 strategy.

It uses two licenced  standard agents but with a higher dose of trastuzumab (6mg per kg) combined with lapatinib to allow higher doses of the drug to be present for 11 days before surgery and induce response.Solid tumours disappearing after 11 days of targeted therapy is unprecedented although it does occur in blood cancers. It is an example of utilising licensed drugs in a novel way to enhance response.

The total number of tumours responding with a 30% fall in Ki67 with the combination of Herceptin and Lapatinib was 85.6% whereas it was only 44% on trastuzumab alone, indicating that not only was the size of the fall in proliferation(tumour switch off)greater but that the number of tumours overall that responded was larger. What should clinicians and patients take away from your report?

Dr. Bundred: Implications are we can potentially individualise or personalise treatment so responding cancers may allow patients to avoid chemotherapy and nonresponding cancers to change therapy.

Currently Herceptin and chemotherapy costs c £20000 but gives everyone treated complications including 5% with cardiac (heart disease) morbidity at 12 months whereas early responders will need less therapy and get less morbidity.

Take home message:-A combination of two different  AntiHER2 therapies Lapatinib and Herceptin induce tumour regression or disappearance in 25% HER2 positive cancers in 11 days. Instead of chemotherapy for 6 months and Herceptin for 12 months after Surgery,it is likely therapy and the duration of therapy can be tailored according to early responses with health and economic benefits to society. Thank you for your contribution to the community.


Abstract presented at the 2016 ECCO-THE EUROPEAN CANCER ORGANISATION

Abstract no: 6 LBA. “Effects of perioperative lapatinib and trastuzumab, alone and in combination, in early HER2+ breast cancer – the UK EPHOS-B trial (CRUK/08/002)”, Thursday, Clinical science symposium: HER2 positive breast cancer, 16.00-17.30 hrs, Elicium.

)Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Professor Nigel Bundred (2016). Combination Treatment Causes Some HER2 Tumors To Regress Quickly