D. Bourgeois

E. Curtit

F. Cognetti

G. Naso

J. Gligorov

R. Masetti

S. Barni

S. Zilberman

English

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190PD Research-based PAM50 predicts risk of relapse in residual diseaseafter anti-HER2 therapiesG. Bianchini1, J. Parker2, L. Carey3, C.M. Perou2, L. Sica1, A. Prat4, T. Pienkowski5, Y-H. Im6, G.V. Bianchi7, T. Ling-Ming8, M-C. Liu9, A. Lluch10, V. Semiglazov11, J. de la Haba-Rodriguez12, D-Y. Oh13, B. Poirier14, J.L. Pedrini15, P. Valagussa16, L. Gianni11Medical Oncology, IRCCS San Raffaele, Milan, Italy, 2Cancer Genetics, University ofNorth Carolina, Chapel Hill, NC, USA, 3Hematology/Oncology, University of NorthCarolina, Chapel Hill, NC, USA, 4Medical Oncology, Hospital Clinic y Provincial deBarcelona, Barcelona, Spain, 5Onkologia Kliniczna, Radomskie Centrum Onkologii,Radom, Poland, 6Sungkyunkwan University School of Medicine, Samsung MedicalCenter, Seoul, Republic of Korea, 7Medical Oncology, Fondazione IRCCS IstitutoNazionale dei Tumori, Milan, Italy, 8Department of Surgery, Taipei Veterans Hospital,Taipei, Taiwan, 9Medical Oncology, Koo Foundation Sun Yat-sen Cancer Center, Taipei,Taiwan, 10Medical Oncology, Hospital Clinico Universitario de Valencia, Valencia, Spain,11Medical Oncology, 14NN Petrov Research Institute of Oncology, St. Petersburg,Russian Federation, 12Medical Oncology, Hospital Reina Sofia, Cordoba, Spain,13Medical Oncology, Seoul National University Hospital, Seoul, Republic of Korea,14Medical Oncology, Centre des Maladies du Sein, Hôpital du Saint-Sacrement, QuebecCity, QC, Canada, 15Department of Surgery, Hospital Ernesto Dornelles, Porto Alegre,Brazil, 16Operative Office, Fondazione Michelangelo, Milan, ItalyBackground: In the NeoSphere trial, we assessed research-based PAM50 subtype pre-dictors at baseline in all patients (pts), and at surgery (SX) in pts with residual disease(RD) to investigate the changes after treatment and the association with pCR and dis-tant event free survival (DEFS).Methods: 417 HER2þ pts were randomized to neoadjuvant TD, TPD, TP or PD(T¼trastuzumab, P¼pertuzumab, D¼docetaxel), and received FAC/FEC and T afterSX. 296 pts had RD. We assessed the intrinsic subtypes, ROR-P and ROR-S in 350(83.9%) and 191 (64.5%) pts at baseline and SX respectively (166 paired samples). Weevaluated the association with pCR and DEFS in the overall population and by ER sta-tus (161 (46.0%) ERþ; 189 (54%) ER-).Results: The intrinsic subtype distribution was different by ER status. After adjustmentfor ER, no significant association with pCR was found. None of the baseline biomarkerswas associated with DEFS in the overall population. In ERþ, Her2-enriched (Her2E)subtype was associated with worst prognosis (HR 3.00 [1.10-8.22]; p¼ 0.032). HigherROR-P and ROR-S were significantly associated with higher risk of recurrence in ERþonly (test for interaction p¼ 0.035 and p¼ 0.012, respectively). At SX, there was a sig-nificant increase in LumA and a decrease in Her2E and LumB subtypes. ROR scoresalso decreased. In ERþ, post-treatment Her2E (HR 7.50 [1.86-30.1]; p¼ 0.044) andLumB (HR 3.12 [1.03-9.94]; p¼ 0.004) subtypes were associated with worst outcomethan LumA. ROR-S and ROR-P were associated with outcome in ERþ tumors only(significant test for interaction). Compared to low-ROR-S group, high (HR 10.5 [2.79-39.3]; p¼ 0.0005) and median (HR 3.52 [1.11-11.4]; p¼ 0.032) groups had higherrecurrence risk. Five year-DEFS was 94%, 78% and 50% in the low, median and highROR-S groups, respectively. In paired samples, the post-treatment biomarker assess-ment was more informative than at baseline.Conclusions: In the NeoSphere study, PAM50 provides different prognostic informa-tion in ERþ and ER- tumors. Pre-treatment biomarkers were less informative thanpost-treatment, reflecting their dynamic modulation. In ERþ tumors with RD,PAM50-derived scores assessed on surgical samples might identify patients who needtreatment escalation. This warrants independent validation.Legal entity responsible for the study: Fondazione Michelangelo.Funding: Has not received any funding.Disclosure: G. Bianchini: Consultant or advisory board member: Roche, EISAI, Pfizer,AstraZeneca, Novartis, MSD, Lilly, Amgen. C.M. Perou: Equity stock holder, consultant,and Board of Director Member: BioClassifier LLC; Listed an inventor on patent applica-tions on the Breast PAM50 assay. A. Prat: Consultancy: Pfizer, Eli Lilly, Novartis,Nanostring Technologies Research funding Novartis, Nanostring Technologies; Scientificadvisory board: Oncolytics Biotech. L. Gianni: Consultant or advisor board member:Roche, Pfizer, Boehringer Ingelheim, Celgene, Tahio Pharmaceutical, Synthon,AstraZeneca, Genomic Health, Merck Sharp & Dohme, Synaffix, Eli Lilly, OdonateTherapeutics, Sandoz, Onkaido, Oncolytics Biotech, ADC Therapeutics, Seattle Genetics.All other authors have declared no conflicts of interest.192PD Randomized trial of lisinopril or carvedilol for the prevention ofcardiotoxicity in patients with early stage HER2-positive breastcancer receiving trastuzumabP.N. Munster1, J. Krischer2, R. Tamura2, L. Bello-Matricaria2, A. Fink2, W. McCaskill-Stevens3, M. Guglin41Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA,USA, 2Health Informatics Institute, University of South Florida, Tampa, FL, USA,3Prevention, National Cancer Institute Div. Cancer Treatment, Rockville, MD, USA,4Cardiology, University of Kentucky, Lexington, KY, USABackground: Trastuzumab is an integral part of therapy for patients with HER2-posi-tive breast cancer. Yet, cardiac side effects, particularly in patients who receive anthra-cyclines require frequent monitoring and result in dose interruptions anddiscontinuation of trastuzumab. Prophylactic use of angiotensin converting enzymeinhibitors or beta blockers may prevent cardiotoxicity associated with chemotherapyand trastuzumab.Methods: In a large prospective double-blind, placebo-controlled trial, the rates of pre-specified cardiotoxicity and trastuzumab interruptions were evaluated in patients withearly stage HER2 positive breast cancer treated with one year of trastuzumab. Patientswere randomized to simultaneously receive either the ACE inhibitor, lisinopril, orbeta-blocker, carvedilol, or placebo and were stratified by anthracycline use.Results: The study included 468 eligible patients (median age:51, BMI:27 kg/m2, base-line systolic BP: 126mmHg and LVEF: 63 6 6.29%) from 127 community-based practi-ces. Both interventions reduced trastuzumab interruptions (p¼ 0.01). For patientsreceiving an anthracycline, cardiac event rates were higher in the placebo group (47%),compared to lisinopril (37%), and carvedilol (31%). Interruptions of trastuzumabwere required in 23% patients on lisinopril and 20% on carvedilol compared to 40% onplacebo (p¼ 0.007). Changes in LVEF from baseline (least square means, SE) were sig-nificantly reduced with both carvedilol (-4.5 (0.8), p¼ 0.008, and lisinopril (-4.0 (0.8),p¼ 0.002) than placebo, (-7.7 (0.8). Cardiotoxicity-free survival was longer on bothcarvedilol (hazard ratio 0.49, 95% confidence intervals 0.27, 0.89, p¼ 0.009) or lisino-pril (HR 0.53, CI 0.30, 0.94, p¼ 0.015). Cardiac events for patients treated with non-anthracycline containing regimens were similar for all groups with no difference innumber of trastuzumab interruptions.Conclusions: Both lisinopril and carvedilol prevented cardiotoxicity in patients withHER2-positive breast cancer treated with trastuzumab and anthracyclines. The use oflisinopril or carvedilol should be considered to offset cardiac events and to minimizeinterruptions of trastuzumab.Clinical trial identification: NCT01009918.Legal entity responsible for the study: National Cancer Institute, CommunityOncology and Prevention Trials Research Group, Rockville, MD.Funding: National Cancer Institute, Community Oncology and Prevention TrialsResearch Group, Rockville, MD.Disclosure: All authors have declared no conflicts of interest.194P Real-life utilization of genomic testing for invasive breast cancerpatients in Italy and France reduces chemotherapy recommendationsS. Barni1, E. Curtit2, F. Cognetti3, D. Bourgeois4, R. Masetti5, S. Zilberman6, G. Naso7,J. Gligorov81Oncology, Azienda Ospedaliera Treviglio-Caravaggio, Treviglio, Italy, 2MedicalOncology, CHU Besançon, Hôpital Jean Minjoz, Besançon, France, 3Medical Oncology,Istituto Regina Elena, Rome, Italy, 4Medical Oncology, ARETASC - Clinique Hartmann,Neuilly-sur-Seine, France, 5Surgical Oncology, Policlinico Universitario Agostino Gemelli,Rome, Italy, 6Surgical Gynecology, Hôpital Tenon, Paris, France, 7Medical Oncology,Policlinico Umberto I, Rome, Italy, 8Medical Oncology APHP, CancerEst, TenonUniversity Hospital, Paris, FranceBackground: Oncotype DXVR (ODX) is a multigene assay allowing physicians to tailortreatment in HRþ, HER2- early-stage breast cancer patients. Clinical validation andutility of ODX have been demonstrated across multiple studies in over 63,000 breastcancer patients worldwide. It provides level 1A evidence and has been incorporated inmajor international clinical guidelines. A market access program was initiated in 2015in France and 2016 in Italy to assess real-life test utilization and its impact in currentclinical practice.Methods: The program allows for prospective data collection reflecting real life use ofODX by physicians in various clinical practice settings throughout France and Italy.Patient data were collected through an online dedicated platform including classicalpathological and clinical parameters (e.g. histology, tumor grade and size, ER, PR,HER2 and Ki67), patient age, ODX Recurrence Score (RS) Results and recommendedtreatment both before and after the test results have been reported.Results: A total of 53 and 19 qualified breast cancer centers, in France and Italy respec-tively, participated in the program and collected 2632 case reports. Study results dem-onstrated that ODX is used among a wide variety of patient profiles: 24% N1, 7% Nmic& 69% N0, 11% G1, 64% G2 and 25% of G3, 32% pre-, 8% peri- & 59% are post-meno-pausal, 34% are 35-50, 52% 51-70 and 13% are older than 70, 13% have Ki67%<10%,35% KI67 10-20%, 30% KI67 21-30% & 18% Ki67>30%, 12% tumor<1cm, 59% 1-2cm and 27% tumor 2.1-5cm. RS distribution is the following:<18 (56%), 18-30(35%) and>30 (9%). In addition, pre-ODX 60% and 48% patients had a treatmentrecommendation for chemo-hormonotherapy (CT-HT) in France and Italy respec-tively. Post-testing, the number of patients recommended CT-HT decreased to 29%and 31% for France and Italy respectively, highlighting that the test reduced unneces-sary use of CT and homogenized treatment decisions.Conclusions: In France and Italy, the use of the ODX test results in an overall reductionin CT recommendations, while also identifying patients more likely to benefit from CT.Legal entity responsible for the study: Genomic Health SARL.Funding: Genomic Health SARL.Disclosure: S. Barni, F. Cognetti: Medical Consultant: Genomic Health. All otherauthors have declared no conflicts of interest.Annals of Oncology abstractsVolume 29 | Supplement 8 | October 2018 doi:10.1093/annonc/mdy270 | viii61Downloaded from https://academic.oup.com/annonc/article-abstract/29/suppl_8/mdy270.189/5142059 by guest on 11 April 2019

194preal life utilization of genomic testing for invasive breast cancer patients in italy and france reduces chemotherapy recommendations

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194preal life utilization of genomic testing for invasive breast cancer patients in italy and france reduces chemotherapy recommendations

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