The prognostic performance of PREDICT+ in patients (pts) with HER2-positive (HER2+) early-stage breast cancer (EBC).

person Elisa Agostinetto Institut Jules Bordet and Université Libre de Bruxelles (U.L.B), Brussels, Belgium info_outline Elisa Agostinetto, Lieveke Ameye, Samuel Martel, Philippe Georges Aftimos, Noam Ponde, Christian Maurer, Sarra El-Abed, Yingbo Wang, Maria Lourdes Vicente, Saranya Chumsri, Judith Bliss, Judith R. Kroep, Marco Colleoni, Fausto Petrelli, Lucia Del Mastro, Alvaro Moreno-Aspitia, Martine J. Piccart-Gebhart, Marianne Paesmans, Evandro de Azambuja, Matteo Lambertini

Authors person Elisa Agostinetto Institut Jules Bordet and Université Libre de Bruxelles (U.L.B), Brussels, Belgium info_outline Elisa Agostinetto, Lieveke Ameye, Samuel Martel, Philippe Georges Aftimos, Noam Ponde, Christian Maurer, Sarra El-Abed, Yingbo Wang, Maria Lourdes Vicente, Saranya Chumsri, Judith Bliss, Judith R. Kroep, Marco Colleoni, Fausto Petrelli, Lucia Del Mastro, Alvaro Moreno-Aspitia, Martine J. Piccart-Gebhart, Marianne Paesmans, Evandro de Azambuja, Matteo Lambertini Organizations Institut Jules Bordet and Université Libre de Bruxelles (U.L.B), Brussels, Belgium, Data Centre, Institut Jules Bordet - Université Libre de Bruxelles (ULB), Brussels, Belgium, CISSS Montérégie-Centre/Hôpital Charles-Le Moyne, Université de Sherbrooke, Greenfield Park, QC, Canada, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium, AC Camargo Cancer Center, São Paulo, Brazil, University of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Cologne, Germany, Breast International Group, Brussels, Belgium, Novartis Pharma AG, Basel, Switzerland, Institut Jules Bordet, Brussels, Belgium, Mayo Clinic, Jacksonville, FL, The Institute of Cancer Research, Clinical Trials & Statistics Unit, London, United Kingdom, Leiden University Medical Center, Leiden, Netherlands, IEO, European Institute of Oncology IRCCS, Milan, Italy, Oncology Department, ASST Bergamo Ovest, Treviglio, Italy, Breast Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, Genoa, Italy Abstract Disclosures Research Funding Other Grant (number 2018-09) from Les Amis de l'Institut Bordet, submitted by P. Aftimos (title: The prognostic performance of PREDICT + in breast cancer patients with early-stage HER2-positive disease in the ALTTO trial). Background: PREDICT+ is a widely used, free, online tool based on traditional clinico-pathological features, including HER2, developed to predict individual mortality of EBC pts and to aid clinical decision making for adjuvant therapy. However, its prognostic role in HER2+ EBC pts treated with chemotherapy (CT) and anti-HER2 therapies remains unclear. We aimed to investigate the prognostic performance of PREDICT+ in HER2+ EBC pts enrolled in the ALTTO trial. Methods: ALTTO is a phase III study evaluating adjuvant lapatinib (L) +/- trastuzumab (T) vs. T alone in pts with HER2+ EBC. Pts enrolled in the ALTTO trial and receiving T-based therapy started concurrently with CT were eligible for this analysis. We calculated PREDICT+ estimates using variables extracted from ALTTO database, blinded to pts outcomes. The prognostic performance of PREDICT+ was evaluated by assessing its calibration and discriminatory accuracy. For calibration, median predicted 5-year (5-yr) overall survival (OS) was compared to observed 5-yr OS. For discriminatory accuracy, the area under the receiver-operator characteristic (AUC under the ROC) curve and corresponding 95% confidence intervals (CI) for predicted 5-yr OS were calculated. Subgroup analyses were performed according to type of anti-HER2 therapy, type of CT, age, hormone receptor (HR) status, nodal status and tumor size. Results: This analysis included 2,794 pts. After a median follow-up of 6.0 years (IQR, 5.8-6.7), 182 deaths were observed. Overall, PREDICT+ underestimated 5-yr OS by 6.7% (95% CI, 5.8-7.6): observed 5-year OS was 94.7% vs. predicted 88.0%. The underestimation was consistent across all subgroups (Table). For discriminatory accuracy, AUC under the ROC curve was 73.7% (95%CI 69.7-77.8) in the overall population, ranging between 61.7% and 77.7% across the analysed subgroups. Conclusions: In HER2+ EBC pts enrolled in the ALTTO trial, the PREDICT+ score highly underestimated OS. The low performance of this prognostic tool was consistent across all pts subgroups. PREDICT+ should be used with caution to give prognostic estimation in HER2+ EBC pts treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies. Calibration according to subgroups. (Predicted – Observed) 5-yr OS (%) (95% CI) Anti-HER2 Therapy L + T -7.0 (-8,5 -5,5) T alone -6,3 (-7,8 -4,7) T → L -6,8 (-8,3 -5,4) CT Non anthracycline-based -8,1 (-10,3 -5,9) Anthracycline-based -6,6 (-7,5 -5,6) Age ≤40 -5,2 (-7,1 -3,4) 41-64 -6,7 (-7,7 -5,7) ≥65 -9,7 (-12,9 -6,6) HR status Negative -13.0 (-14,4 -11,5) Positive -2,7 (-3,7 -1,7) Number of N+ 0 -6,1 (-7,4 -4,9) 1-3 -9.0 (-10,2 -7,8) >3 -15,8 (-18,3 -13,3) Tumor size (mm) ≤20 -6,2 (-7,1 -5,3) 21-50 -7,3 (-8,7 -6.0) >50 -15,3 (-20,4 -10,2)