Moving from adjuvant to neoadjuvant trials for development of new therapies in breast cancer: a hopeless heresy or a feasible paradigm shift?

Transcription

1 XII Michelangelo Foundation Seminar Scientific programme Milan, October 12, 2012 Hotel Michelangelo h Moving from adjuvant to neoadjuvant trials for development of new therapies in breast cancer: a hopeless heresy or a feasible paradigm shift?

2 XII Michelangelo Foundation Seminar Moving from adjuvant to neoadjuvant trials for development of new therapies in breast cancer: a hopeless heresy or a feasible paradigm shift?

3 Milan, October 12, 2012 Hotel Michelangelo Michelangelo Hall h FACULTY Patricia Cortazar, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, USA Carsten Denkert, Institute of Pathology, Charité Hospital, Campus Mitte, Berlin, Germany Luca Gianni, Department of Medical Oncology, IRCCS Istituto Scientifico San Raffaele, Milan, Italy Stephen Johnston, Professor of Breast Cancer Medicine and Consultant Medical Oncologist and Director of Clinical Research & Development at the Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London UK Lajos Pusztai, Department of Breast Medical Oncology, Yale Cancer Center, New Haven, USA Gunter von Minckwitz, Universitäts-Frauenklinik Frankfurt & German Breast Group, GBG Forschungs GmbH, Neu-Isenburg, Germany Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, USA

4 The goals of neoadjuvant therapy of breast cancer have significantly changed and evolved since it was firstly applied to women with inoperable locally advanced and inflammatory breast cancers XII Michelangelo Foundation Seminar in the early 1970 s. The extended indication to allow more breast conserving surgery has widened the application of neoadjuvant treatments and provided evidence for the association between favorable long term outcome and intermediate endpoints, like pathologic complete response (pcr) after chemotherapy or decreased tumor proliferation measured by Ki67 after endocrine therapy. A key question is whether pcr and Ki67 can take the role of qualified and validated surrogate markers of drug efficacy, so that any difference in survival between treatments disappeared after adjustment for the intermediate endpoint. The recent improvements in understanding the molecular basis of breast cancer heterogeneity has provided a new level of complexity but also an outstanding conceptual framework for interpreting the role of pcr as potential surrogate marker, and has made clear that the biologic meaning of pcr is different in different molecular subtypes, and that different molecular subtypes will require different intermediate surrogate endpoints. The validation of the intermediate surrogates markers of efficacy would dramatically change the landscape of development of new drugs for early breast cancer and provide the rationale for a comparative analysis of the intermediate endpoint instead of the final survival endpoint. The feasibility of this major paradigm shift from large and lengthy adjuvant clinical trials to smaller and faster neoadjuvant trials will be the topic of discussion of this seminar, and will be addressed by regulators, biostatisticians, translational scientists and oncologists.

5 Milan, October 12, 2012 Hotel Michelangelo Michelangelo Hall h SCIENTIFIC PROGRAMME Welcome address and introductory notes Prediction of benefit from response, pcr and biomarkers and the challenge of breast cancer heterogeneity L. Pusztai, New Haven, USA Neoadjuvant endocrine therapy and Ki67 as surrogate marker of efficacy: can we trust it? S. Johnston, London, UK Neoadjuvant chemotherapy and targeted therapy: when pcr matters? The German Breast Group experience G. von Minckwitz, Neu-Isenburg, D - C. Denkert, Berlin, D Neoadjuvant chemotherapy and targeted therapy: when pcr matters? The NSABP Experience N. Wolmark, Pittsburgh, USA The opportunity of the neoadjuvant approach L. Gianni, Milan, I Paradigm shift? The Food and Drug Administration collaborative project P. Cortazar, Silver Spring, USA General discussion and conclusion

6 XII Michelangelo Foundation Seminar GENERAL INFORMATION Seminar Venue Hotel Michelangelo - Michelangelo Hall Via Scarlatti, Milan Italy CME Accreditation Applications to the competent bodies will be made to obtain approval for Italian CME accreditation for Physicians, Biologists, Nurses and Chemists Official Language The official languages will be English. Simultaneous translation provided CME Provider and Organizing Secretariat Effetti srl Via Gallarate, Milan I Phone Fax Mail: michelangelo@effetti.it Scientific Secretariat Mail to: michelangelo@effetti.it Giampaolo Bianchini, IRCCS Istituto Scientifico San Raffaele, Milan, I Fabio Puglisi, University Hospital of Udine, I

7 ACKNOWLEDGEMENTS The Faculty, the Scientific and Organizing Secretariat wish to thank the following Companies for support given, in the form of unrestricted educational grants:

8 Fondazione Michelangelo Via Venezian, Milan, I Tel Fax