A. Ferro

A. Frassoldati

A. Maiorana

A. Musolino

A. Rimanti

A.A. Brandes

C. Omarini

E. Bertone

E. Orvieto

F. Giotta

G. Bisagni

K. Cagossi

L. Cavanna

M. Sanders

M.V. Dieci

O. Garrone

P.F. Conte

R. D'Amico

S. Sarti

V. Guarneri

English

Maria Vittoria Dieci

Pierfranco Conte

G Bisagni

A A Brandes

A Frassoldati

L Cavanna

A Musolino

F Giotta

A Rimanti

O Garrone

E Bertone

K Cagossi

S Sarti

A Ferro

C Omarini

A Maiorana

E Orvieto

M Sanders

R D'Amico

Valentina Guarneri

Archivio istituzionale della ricerca - Università di Padova

186O Tumor-infiltrating lymphocytes (TILs) as an independent prognostic factor for early HER2+ breast cancer patients treated with adjuvant chemotherapy and trastuzumab in the randomized shortHER trial

Dieci, M. V.

Conte, P. F.

Bisagni, G.

Brandes, A. A.

Frassoldati, A.

Cavanna, L.

Musolino, A.

Giotta, F.

Rimanti, A.

Garrone, O.

Bertone, E.

Cagossi, K.

Sarti, S.

Ferro, A.

Omarini, C.

Maiorana, A.

Orvieto, E.

Sanders, M.

D'Amico, R.

Guarneri, V.

Archivio istituzionale della Ricerca -  Università degli Studi di Parma

Tumor-infiltrating lymphocytes (TILs) as an independent prognostic factor for early HER2+ breast cancer patients treated with adjuvant chemotherapy and trastuzumab in the randomized shortHER trial

Open Access Repository

184O Distant disease-free survival (DDFS) according to response category inneoadjuvant endocrine therapy (NET): 6-year analysis in phase IIINEOS trialH. Iwata1, N. Masuda2, Y. Yamamoto3, T. Fujisawa4, T. Toyama5, N. Taira6,M. Kashiwaba7, S. Ohtani8, T. Sakai9, Y. Hasegawa10, R. Nakamura11, H. Akabane12,Y. Shibahara13, H. Sasano13, T. Yamaguchi14, Y. Ohashi15,1Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan, 2Surgery, NHO OsakaNational Hospital, Osaka, Japan, 3Breast Surgery, Kumamoto University, Kumamoto,Japan, 4Breast Surgery, Gunma Prefectural Cancer Center, Gunma, Japan, 5BreastSurgery, Nagoya City University, Aichi, Japan, 6Breast Surgery, Okayama UniversityHospital, Okayama, Japan, 7Breast Surgery, Sagara Hospital, Kagoshima, Japan, 8BreastSurgery, Hiroshima City Hospital, Hiroshima, Japan, 9Surgical Oncology, CancerInstitute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan, 10BreastSurgery, Hirosaki Municipal Hospital, Hirosaki, Japan, 11Breast Surgery, Chiba CancerCenter Hospital, Chiba, Japan, 12Surgery, Hokkaido P.W.F.A.C. Asahikawa-Kosei GeneralHospital, Hokkaido, Japan, 13Pathology, Tohoku University Graduate School ofMedicine, Sendai, Japan, 14Statisticus, Tohoku University Graduate School of Medicine,Sendai, Miyagi, Japan, 15Integrated Science and Engineering for Sustainable Society,Chuo University, Tokyo, JapanBackground: NEOS is a randomized phase III study that assessed the long-term prog-nosis of estrogen receptor positive (ERþ) primary breast cancer (PBC) pts whoreceived NET with/without adjuvant chemotherapy (CT). We presented the first reportabout the relationship between DFS and clinical response to NET at median follow-up4Y in SABCS 2017. We now present new data corrected according to long follow-up(median 5.9Y).Methods: Postmenopausal BC pts with ERþ/HER2 negative, T1c-2, clinically nodenegative, and under 76 years old were enrolled at primary registration. Pts were treatedby leterozole (LET) in weeks 24-28 after primary enrollment. Pts who experienced pro-gression of disease (PD) during neoadjuvant phase were excluded at randomizationand received systemic therapy driven by investigators before or after surgery. Pts whomet eligibility criteria were randomized 1:1 to LET for 4.5-5 years after CT or LET alonefor 4.5-5 years without CT after surgery. DFS/OS in patients showing CR, PR, SD or PDresponse to NET are secondary endpoints and DDFS is an exploratory endpoint.Results: Between May 2008 and June 2013, 904 patients were enrolled at primary regis-tration from 100 institutions in Japan and 21 pts were withdrawn during neoadjuvantphase. The median age was 63 years, T1c: 36%, T2: 64%, and progesterone receptor(PgR)þ: 79%. Clinical response rates (CR, PR, SD and PD) were 2% (16pts), 48%(421pts), 46% (403pts) and 5% (43pts), respectively. In each response, 0% (0/16),10.7% (45/421), 12.7% (51/403), and 44.2% (19/43) experienced DFS events and 0%(0/16), 5.2% (22/421), 7.2% (29/403) and 26% (11/43) experienced DDFS events.DDFS in PD pts to NET were statistically significantly worse than CR, PR, SD pts(p< 0.001, hazard ratio 4.83 (95% CI:2.52-9.29). The predictive markers of PD forNET were PgR status (P< 0.001) and Ki67 status (P¼ 0.041) in biopsy specimenamong factors evaluated by multivariate analysisConclusions: The DDFS of PBC pts excluding PD pts to NET is excellent regardless oftreatment with/without CT. NET with utilization of PD response as a prognosticmarker can be considered as a standard treatment option for these patients.Clinical trial identification: UMIN000001090.Legal entity responsible for the study: CSPOR.Funding: The parent NEOS study was sponsored by CSPOR (Comprehensive SupportProject for Oncology Research), part of a Sponsored by CSPOR and Novartis andChugai Pharmaceuticals provided funding to CSPOR.Disclosure: H. Iwata: Research: Chugai, Novartis, MSD, Lilly; Honororia: Chugai,AstraZeneca, Daiichi Sankyo; Advisory Board: Daiichi Sankyo, Chugai, Lilly, KyowaHakko Kirin, Pfizer, Novartis, AstraZeneca. N. Masuda: Honoraria: Chugai,AstraZeneca, Pfizer, Takeda; Research: Chugai, Novartis, MSD, Eli-Lilly, AstraZeneca,Daiichi Sankyo, Kyowa- Kirin, Pfizer. T. Toyama: Research fund: Eisai, Kyowa Kirin,Takeda, Chugai, Novartis, Nippon Kayaku, Pfizer, Daiichi Sankyo; Advisory board:AstraZeneca. M. Kashiwaba: Honoraria: Chugai, AstraZeneca. Y. Ohashi: Honororia:Chugai, PHRF; Consultant: Chugai; Research fund: Eisai. All other authors havedeclared no conflicts of interest.186O Tumor-infiltrating lymphocytes (TILs) as an independent prognosticfactor for early HER21 breast cancer patients treated with adjuvantchemotherapy and trastuzumab in the randomized shortHER trialM.V. Dieci1, P.F. Conte1, G. Bisagni2, A.A. Brandes3, A. Frassoldati4, L. Cavanna5,A. Musolino6, F. Giotta7, A. Rimanti8, O. Garrone9, E. Bertone10, K. Cagossi11, S. Sarti12,A. Ferro13, C. Omarini14, A. Maiorana15, E. Orvieto16, M. Sanders17, R. D’Amico18,V. Guarneri11Department of Surgery, Oncology and Gastroenterology, University of Padova, IstitutoOncologico Veneto IRCCS, Padua, Italy, 2Medical Oncology, Azienda OspedalieraArcispedale Santa Maria Nuova - IRCCS, Reggio Emilia, Italy, 3Medical Oncology,Ospedale Bellaria, Bologna, Italy, 4Clinical Oncology, Azienda Ospedaliera di Ferrara St.Anna, Ferrara, Italy, 5Oncology Department, Azienda Ospedaliera di Piacenza,Piacenza, Italy, 6Medical Oncology, Azienda Ospedaliera di Parma, Parma, Italy,7Medical Oncology, Istituto Oncologico Bari, Bari, Italy, 8Oncology, Azienda Ospedalieradi Mantova, Mantova, Italy, 9Medical Oncology, Azienda Ospedaliera St. Croce e Carle,Cuneo, Italy, 10Medical Oncology, S. Anna Hospital, Turin, Italy, 11Medical Oncology,Ramazzini Hospital, Carpi, Italy, 12Medical Oncology, Istituto Tumori della RomagnaI.R.S.T., Meldola, Italy, 13Medical Oncology, Ospedale Santa Chiara, Trento, Italy,14Medical and Surgical Sciences for Children & Adults, Universita degli Studi di Modenae Reggio Emilia, Modena, Italy, 15Diagnostic and Clinical Medicine and of PublicHealth, University of Modena and Reggio Emilia, Modena, Italy, 16Pathology, ULSS 5Polesana, Rovigo, Italy, 17Pathology, Microbiology, and Immunology, VanderbiltUniversity Medical Center, Nashville, TN, USA, 18Department of Diagnostic and ClinicalMedicine and Public Health, University Hospital of Modena and Reggio Emilia, Modena,ItalyBackground: TILs are an established prognostic factor for triple negative breast cancer.We investigated the prognostic role of TILs for HER2þ early breast cancer patientsenrolled in the prospective ShortHER trial.Methods: The ShortHER study randomized 1254 patients with HER2þ early breastcancer to receive 9 weeks vs 1 year of adjuvant trastuzumab combined with chemother-apy (Conte, ASCO 2017). TILs were assessed for 855 cases on centralized HES slidesaccording to recommendations (Salgado, Ann Oncol 2015). Metastasis-free survival(MFS) was calculated from randomization to distant disease recurrence or death.Median follow up was 72 months.Results: Median TILs was 5% (Q1-Q3 1%-15%). Higher TILs were associated withhormone receptor-negative status (p< 0.001) and age<60 years (p¼ 0.008). Therewas no association with stage and PIK3CA mutation. Increased TILs were associatedwith better MFS (HR 0.69, 95%CI 0.54-0.88 for each 10% TILs increment, p¼ 0.003).5-yrs MFS rates were 91%, 94% and 100% for TILs<20%, TILs>¼20% &<50% andTILs>¼50% (p¼ 0.013). Multivariable cox models confirmed TILs as independentprognostic factor (Table).Table: 186OMULTIVARIATE COX MODELS FOR MFSFactors All patients HormoneReceptor negHormoneReceptor posHR(95% CI)p HR(95% CI)p HR(95% CI)pTILs 10% increase 0.67(0.52-0.86)0.001 0.72(0.53-0.97)0.031 0.57(0.36-0.91)0.017HR pos vs neg 0.63(0.39-1.00)0.049 - - - -Stage I-II vs III 0.31(0.20-0.50)<0.001 0.27(0.13-0.59)0.001 0.33(0.19-0.60)<0.001Age >60 vs< 60 1.02(0.65-1.60)0.936 1.44(0.69-3.02)0.337 0.82(0.45-1.47)0.501The association between 10% TILs increments and MFS was significant in the short(HR 0.49, 95%CI 0.29-0.82, p¼ 0.006) but not in the long arm (HR 0.84, 95%CI 0.65-1.10, p¼ 0.212). Patients with TILs<20% benefitted from long treatment (HR 0.76,95%CI 0.60-0.97, p¼ 0.024), whereas for patients with TILs>¼20% the HR favoredthe short arm (HR 2.79, 95%CI 0.98-7.96, p¼ 0.055; 8 events only). Interaction testVC European Society for Medical Oncology 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology.All rights reserved. For permissions, please email: journals.permissions@oup.com.Annals of Oncology 29 (Supplement 8): viii58–viii86, 2018doi:10.1093/annonc/mdy270BREAST CANCER, EARLY STAGEDownloaded from https://academic.oup.com/annonc/article-abstract/29/suppl_8/mdy270.183/5141973 by guest on 19 November 2018showed p¼ 0.064 (arm*10% TILs increase) and p¼ 0.019 (arm*TILs binary variablewith 20% cutoff).Conclusions: TILs are an independent prognostic factor for HER2þ early breast cancerpatients treated with adjuvant chemotherapy and trastuzumab. Integration of TILs inprognostic algorithms can help refining risk stratification and guiding therapeutic de-escalation.Clinical trial identification: EudraCT 2007-004326-25 Start date: 2007-11-15.Legal entity responsible for the study: University of Modena and Reggio Emilia;University of Padova.Funding: Agenzia Italiana del Farmaco (AIFA).Disclosure: P.F. Conte: Speaker’s bureau: Roche Genentech; Research funding(Institution): Roche. V. Guarneri: Research funding (Institution): Roche. All otherauthors have declared no conflicts of interest.187O High-dose chemotherapy (HDCT) with hematopoietic stem celltransplantation (HSCT) in high-risk breast cancer (BC) patients with 4involved axillary lymph nodes (ALN): 20-year follow-up of arandomized phase 3 studyT.G. Steenbruggen1, L.C. Steggink2, C.M. Seynaeve3, J.J.M. van derHoeven4, M.J. Hooning5, A. Jager3, I.R. Konings6, J.R. Kroep7, W.M. Smit8, V.C.G. Tjan-Heijnen9, E. van der Wall10, A.D. Bins11, S.C. Linn1, M. Schaapveld12, F.E. van Leeuwen12,C.P. Schroder2, H. van Tinteren13, E.G.E. de Vries2, G.S. Sonke1, J.A. Gietema21Medical Oncology, The Netherlands Cancer Institute Antoni van LeeuwenhoekHospital, Amsterdam, Netherlands, 2Medical Oncology, University Medical CenterGroningen, Groningen, Netherlands, 3Medical Oncology, Erasmus MC Daniel den HoedCancer Center, Rotterdam, Netherlands, 4Medical Oncology, Radboud University,Nijmegen, Netherlands, 5Department of Medical Oncology, Family Cancer Clinic,Erasmus MC Cancer Institute, Rotterdam, Netherlands, 6Medical Oncology, VrijeUniversity Medical Centre (VUMC), Amsterdam, Netherlands, 7Medical Oncology, LeidenUniversity Medical Center (LUMC), Leiden, Netherlands, 8Medical Oncology, MedischSpectrum Twente (MST), Enschede, Netherlands, 9Medical Oncology, MaastrichtUniversity Medical Center (MUMC), Maastricht, Netherlands, 10Cancer Center, UMC -University Medical Center Utrecht, Utrecht, Netherlands, 11Medical Oncology, AcademicMedical Center (AMC), Amsterdam, Netherlands, 12Epidemiology, Netherlands CancerInstitute/Antoni van Leeuwenhoek hospital (NKI-AVL), Amsterdam, Netherlands,13Biostatistics, Het Nederlands Kanker Instituut Antoni van Leeuwenhoek (NKI-AVL),Amsterdam, NetherlandsBackground: Adjuvant HDCT for high-risk BC is not beneficial overall compared toconventional chemotherapy at the cost of considerable toxicity. HDCT benefit, how-ever, may be present in very high-risk patients (i.e.>9 involved ALN) and in triple neg-ative (TN) BC patients, although long-term results are lacking for most initial studies.We evaluated long-term outcome of a randomized phase 3 study, conducted from 1993to 99.Methods: Patients aged<56 years with early BC and4 involved ALN were random-ized to either conventional chemotherapy or HDCT as adjuvant systemic treatment.The conventional arm consisted of 5x fluorouracil, epirubicin and cyclophosphamide(FEC) 3-weekly. In the HDCT arm, the 5th FEC was replaced by cyclophosphamide6000 mg/m2, thiotepa 480 mg/m2, carboplatin 1600 mg/m2 and supported with autolo-gous HSCT (Rodenhuis, NEJM 2003). We collected 20-year follow-up data from medi-cal records, general practitioners, and the Netherlands Cancer Registry. Endpoints wererelapse free survival (RFS), overall survival (OS), BC specific survival (BCSS), and safetybased on intention to treat analyses.Results: 885 patients (64% 4-9 ALN, 36%>9 ALN; 53% ERþ/HER2-, 23% HER2þ,16% TN, 8% unknown) were randomized to FEC (n¼ 443) or HDCT (n¼ 442). Thetable shows efficacy results of univariable Cox models. With 20 years median follow-up, relapse or death occurred in 272 patients (61%) who received FEC vs in 257 (58%)HDCT patients (HR 0.88; 95% CI 0.74-1.05). The effect of HDCT compared to FECwas most pronounced in patients with>9 involved ALN and in TNBC patients. In 138TNBC patients the 20-year OS estimate was 52% after HDCT vs 39% after FEC. Long-term safety and BCSS will also be presented at the meeting.Table: 187ORFS HDCT FECN 20 yr (%) 95% CI 20 yr (%) 95% CI HR 95% CI pAll 885 42 37-47 38 33-43 0.88 0.74-1.05 0.154-9 ALN 568 43 38-50 44 38-50 1.00 0.81-1.25 0.97>9 ALN 317 39 31-47 27 21-36 0.71 0.54-0.94 0.02ERþ/HER2- 469 40 34-47 36 30-43 0.83 0.66-1.04 0.11HER2þ 205 38 30-49 42 33-52 1.15 0.80-1.63 0.46TN 138 51 40-65 34 24-48 0.66 0.42-1.03 0.07OS HDCT FECN 20 yr (%) 95% CI 20 yr (%) 95% CI HR 95% CI pAll 885 45 41-50 41 37-46 0.89 0.74-1.06 0.184-9 ALN 568 46 40-52 48 42-54 1.01 0.81-1.27 0.91>9 ALN 317 44 37-53 30 23-38 0.72 0.54-0.95 0.02ERþ/HER2- 469 46 40-53 40 34-47 0.81 0.64-1.03 0.09HER2þ 205 40 32-51 46 37-56 1.15 0.80-1.66 0.44TN 138 52 41-65 39 29-52 0.71 0.45-1.12 0.14Conclusions: Long-term follow-up confirms survival benefit of HDCT in BC patientswith>9 involved ALN and suggests benefit in TNBC patients.Clinical trial identification: NCT03087409.Legal entity responsible for the study: High-risk breast cancer study group from theNetherlands Working Party on Autologous Transplantation in Solid Tumors.Funding: Has not received any funding.Disclosure: T.G. Steenbruggen: Financial support: Memidis Pharma unrelated to thesubmitted work. V.C.G. Tjan-Heijnen: Research funding through grants institution:Eisai, Roche, Pfizer, Novartis, and AstraZeneca; Compensation for service as a consul-tant: AstraZeneca, Pfizer, Novartis, and Roche; Honoraria: Pfizer, Roche, and Novartis;Travel expenses: Pfizer, Novartis, and Roche. S.C. Linn: Institutional research funding:AstraZeneca, Amgen, BMS, Genentech, Roche, and Sanofi; Advisory board member:AstraZeneca, Novartis, Roche and Sanofi. E.G.E. de Vries: Consulting/advisory boardfees: Synthon, Pfizer and Sanofi; Grants: Novartis, Amgen, Roche/Genentech,Regeneron, Chugai, Synthon, AstraZeneca, Radius Health, CytomX Therapeutics andNordic Nanovector, all to the hospital and unrelated to the submitted work. G.S.Sonke: Institutional research funding: AstraZeneca, Merck, Novartis, Roche, unrelatedto the submitted work. All other authors have declared no conflicts of interest.193O An international update of the EORTC questionnaire for assessingquality of life in breast cancer patients (EORTC QLQ-BC23) - EORTCQLQ-BR45V. Bjelic-Radisic1, A. Bottomley2, F. Cardoso3, D. Cameron4, E. Brain5, K. Kuljanic6,R.A. de Costa7, T. Conroy8, E. Inwald9, S. Serpentini10, M. Pinto11, J. Weis12, O. Morag13,G. Guro Lindviksmoen Astrup14, K. Tomaszweksi15, K. Pogoda16, P. Sinai17,M.A.G. Sprangers18, N. Aaronson19, E. Greimel201Senology, Helios University Hospital, Wuppertal, Germany, 2QoL, EORTC - EuropeanOrganisation for Research and Treatment of Cancer, Brussels, Belgium, 3Breast Unit,Champalimaud Foundation Cancer Center, Lisbon, Portugal, 4Oncology, EdinburghCancer Centre Western General Hospital, Edinburgh, Midlothian, UK, 5Department ofMedical Oncology, Institut Curie, Paris & Saint-Cloud, France, 6Gynecology, MedicalUniversity Rijeka, Rijeka, Croatia, 7Surgery, HC Barretas, Barretas, Brazil, 8MedicalOncology, ICL Alexis Vautin, Lorraine, France, 9Gynecology, Medical UniversityRegensburg, Regensburg, Germany, 10Oncology, IOV Oncologica Veneto Padova,Padova, Italy, 11Oncology, Instituto Nazionale Tumori Fondazione Pascale Naples,Naples, Italy, 12Oncology, Medical University Freiburg, Freiburg, Germany, 13MedicalOncology, SHEBA_Israel, Tel Aviv, Israel, 14Oncology, Oslo Univ. Hospital, Oslo, Norway,15Surgical oncology, Jagillonian University Medical College Krakow, Krakow, Poland,16Medical Oncology, The Maria Sklodowska Curie Memorial Cancer Centre andInstitute of Oncology (MCMCC), Warsaw, Poland, 17Surgery, University of Bristol, Bristol,UK, 18Department of Medical Psychology, Academic Medical Center (AMC), Amsterdam,Netherlands, 19Psychology, NCI Amsterdam, Amsterdam, Netherlands, 20Gynecology,Medical University Graz, Graz, AustriaBackground: The EORTC QLQ-BR23 was one of the first disease specific questionnairedeveloped in 1996 to assess quality of life (QoL) in patients with breast cancer (BC).However, since 1996, major changes in BC treatment have occurred, requiring updat-ing of the EORTC BC module. This abstract presents the phase I-III study updating theEORTC QLQ-BR23.Methods: The update of the EORTC QLQ-BR23 module followed standard EORTCguidelines. QoL issues relevant for BC patients were generated in the phase I-II. Resultsof an extensive literature systematic review found 83 potential relevant QoL issues.After shortening the issues lists for overlapping, already existing in QLQ-C30 and QLQBR-23 and following by interviews with patients and health care providers, 15 relevantissues were transformed into 27 items. The preliminary module of 27 items was pre-Annals of Oncology abstractsVolume 29 | Supplement 8 | October 2018 doi:10.1093/annonc/mdy270 | viii59Downloaded from https://academic.oup.com/annonc/article-abstract/29/suppl_8/mdy270.183/5141973 by guest on 19 November 2018

tumor infiltrating lymphocytes tils as an independent prognostic factor for early her2 breast cancer patients treated with adjuvant chemotherapy and trastuzumab in the randomized shorther trial

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tumor infiltrating lymphocytes tils as an independent prognostic factor for early her2 breast cancer patients treated with adjuvant chemotherapy and trastuzumab in the randomized shorther trial

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Archivio istituzionale della ricerca - Università di Padova

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