Comparison of HERA and GHEA studies

1. Observational GHEA study: adjuvant-trastuzumab-treatment of HER2-positive breast carcinoma Campiglio M., Tagliabue E., Balsari A., Bufalino R., Ferri E., Ménard S. on the behalf of GHEA (Group of Italian oncologic centers) Fondazione IRCCS ‘Istituto Nazionale dei Tumori’ Milan, Italy Abstract Hera and GHEA disease free survival (HERA median FU= 23.5 (Smith 2007); GHEA median FU = 29 months) Comparison between relapses occurring before (early metastases) or after (late metastases) 18 months from the first trastuzumab treatment Background: GHEA (Group HErceptin in Adiuvant treatment), an Italian multicentric observational study, was designed with the aim to investigate on adjuvant trastuzumab-therapy of HER2-positive breast carcinomas in conventional clinical setting. Material and Methods: Eligible patients should have been treated with trastuzumab in adjuvant setting between 2006 and 2007 and were collected among 35 oncologic Italian centers. Results: The 516 patients registered in the GHEA database had a median age of 52 years and 50% were in post-menopause at the time of trastuzumab therapy, similarly to cohort of patients enrolled in HERA (median age of 49 years and post-menopause status in 46%). Primary breast tumors in GHEA were mainly of ductal type (93%) of high grade (53% were GIII) and small in size (50% T1); 7 % of the samples included in GHEA were classified as N-negative and T1micro, T1a and T1b, and around 4% were T4, four categories not included in HERA. ER-PgR positive tumors were 42%, thus higher than in HERA (31%). Negative lymph-nodes were present in 42% of cases compare to 32% in HERA. Thus, in GHEA study are included earlier breast cancers than in HERA. Moreover, some GHEA cases are not fitting selection criteria of HERA trial, therefore the follow-up of those patients will give us indication of trastuzumab efficacy that are lacking in those categories right now. In the Italian clinical practice the 96% of the patients completed 1 year trastuzumab treatment with around 2% of patients registered cardiac toxicity, considering that also patients with LVEF <55 were included. GHEA DFS at 21 months of FU resulted similar to the one of HERA DFS at 23.5 months of FU. To date, half of patients progressed during trastuzumab treatment with some distant metastasis (i.e. bones, liver, lung, SNC). Discussion: The purpose of the present study is to gather information from a large number of patients related to the effect of adjuvant trastuzumab treatment in conventional clinical setting. Furthermore, the inclusion of patients’ categories not included in clinical trials can be used to design further clinical trials to better define guide-line for trastuzumab adjuvant therapy and for the treatment of these patients at relapse. Supported by AIRC and Roche. Number of patients enrolled in the study have been updated to May 2010 and correspond to 694 patients; analyses presented in the poster are based on this cohort. Site of metastases Bone 22.5 89.0 11.0 All others 77.5 0.005545.8 54.2 0.0466 GHEA patients not eligible according to HERA trial eligibility criteria Comparison of HERA and GHEA studies Table of Participants Hospital Fond. INT Milano Ospedale Infermi (Fantini Manuela) A.S.S. N° 1 Triestina (Mustacchi Giorgio) Policlinico Umberto I (Di Seri Marisa) Humanitas CCO (Aiello Rosa A.) INT Regina Elena (Fabi Alessandra) AO S. Giov. di Dio e R. D'Aragona (Salvastato Clementina) A.O.R.N. Cardarelli (Riccardi Ferdinando) Ist. Onc. Mediterraneo (Giuffrida Dario) Azienda Ospedaliera C. Poma (Cavazzini Giovanna) Osp. Civile So - Az. Osp. Valtellina (Bertolini Alessandro) Ospedale Maggiore - UniVr (Molino Annamaria) Osp San Giovanni Addolorata (Mauri Maria) CRO Aviano (Veronesi Andrea) Istituto Oncologico Veneto (Jirillo Antonio) PO San Giovanni Antica Sede (Airoldi Mario) Istituto Fondazione S. Maugeri (Pavesi Lorenzo) Ospedali Riuniti di Bergamo (Tondini Carlo A.) Ospedale Niguarda Milano (Siena Salvatore) Ospedale Sacco Milano (Piazza Elena) Mangiagalli, R.Elena Milano (Visintin Roberto) Ospedale Misericordia e Dolce (Di Leo Angelo)Ospedale S. Chiara Trento (Frisinghelli Michela)Ospedale di Lecco (Visini Marilena)Fondazione poliambulanza Brescia (Rizzi Anna)IRCCS Multimedica Sesto S. Giovanni (Gottardi Ornella)Ospedale Fatebenefratelli Milano (Farina Gabriella) Metastatic disease: characteristics of patients, tumors and type of treatments Conclusions • The multicenters Italian observational GHEA study includes earlier breast cancers (T1, N- hormone receptors-positive) than HERA trial and accordingly the DFS is improved. • About 20% of cases included in GHEA are not fitting selection criteria of HERA trial, thus FU of those patients will give us indication of trastuzumab efficacy that are lacking in these categories right now. • Relapses have been observed in 55 patients: N-positivity, T>1 and presence of vascular invasion are significantly associated to relapse. • Relapses occuring during or within 6 months from the end of trastuzumab therapy were found to be independent of N and T status and vascular invasion; early metastases were more frequent at the bone level. FONDAZIONE IRCCS ISTITUTO NAZIONALE DEI TUMORI, MILANO *p calculated with Fisher’s exact test