Found 3 Presentations For Request "Fortunato Ciardiello "

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NSCLC, metastatic

1092P - Clinical potential of circulating tumor DNA (ctDNA)-based molecular response (MR) and baseline blood-based tumor mutational burden (bTMB) for monitoring response to first-line (1L) chemoimmunotherapy in advanced squamous non-small cell lung cancer (sqNSCLC)

Presentation Number
1092P
Speakers
  • Fortunato Ciardiello (Napoli, Italy)
Date
Mon, 12.09.2022

Abstract

Background

The clinical utility of ctDNA-based approaches, such as bTMB and MR, to monitor and predict response during chemo-immunotherapy was evaluated using longitudinal cohort samples from a phase IIa study of patients (pts) with advanced sqNSCLC treated with 1L avelumab in combination with cetuximab and chemotherapy (NCT03717155).

Methods

Fifty-two plasma samples were obtained from 21 pts treated with 1L avelumab, cetuximab, gemcitabine, and cisplatin for 4 x 3-week cycles followed by avelumab and cetuximab maintenance. The confirmed best overall response (BOR) per RECIST v1.1 was available for 19 pts. The GuardantOMNI liquid biopsy (LBx) assay was used to detect somatic alterations in 497 genes and generate bTMB from baseline, and MR scores from baseline and day 85. bTMB and somatic alterations influencing response were explored. MR scores were calculated using the validated Guardant Response algorithm. Associations between ctDNA metrics and BOR were assessed.

Results

We detected somatic mutations in 51 of 52 samples. Biomarker-positive pts were defined as those with high bTMB score (≥20 mut/Mb) and/or STK11, KEAP1, LRP1B, ARID1A/1B/2 mutations. Ten of 18 baseline samples were biomarker-positive; all biomarker-positive pts had a BOR of partial response (PR) or stable disease (SD) and no progressive disease (PD). Eight of 18 baseline samples were biomarker-negative, of which 5 had a BOR of PR or SD and 3 had PD. All 3 pts with PD were TMB-low and 1 had a dual STK11/KRAS alteration, which was previously shown to negatively affect the clinical benefit of immunotherapy. The average ctDNA reduction at the tumor assessment visit following day 85 LBx collection for pts with PR/SD was significantly greater than for pts with PD (82% vs 57%; P=.032).

Conclusions

We showed that plasma ctDNA analysis supported MR assessment in pts treated with avelumab combination therapy, which could indicate its clinical utility as an adjunct to RECIST in monitoring tumor response. Plasma TMB-high combined with defined somatic mutations was associated with avelumab combination benefit. Prof. F. Ciardiello and Dr. Z. Feng are acknowledged as first authors and equal contributors to this abstract.

Clinical trial identification

NCT03717155.

Editorial acknowledgement

Editorial support was provided by Abhijith Thippeswamy of ClinicalThinking, and was funded by Merck (CrossRef Funder ID: 10.13039/100009945) as part of an alliance between Merck and Pfizer.

Legal entity responsible for the study

Merck, as part of an alliance between Merck and Pfizer.

Funding

Merck (CrossRef Funder ID: 10.13039/100009945), as part of an alliance between Merck and Pfizer.

Disclosure

F. Ciardiello: Financial Interests, Institutional, Research Grant: Merck, Amgen, Roche; Financial Interests, Personal, Advisory Role: Merck, Amgen, Roche, MSD, Pierre Fabre, Servier. Z. Feng: Financial Interests, Personal, Full or part-time Employment: Merck. N.R. Smith: Financial Interests, Personal, Other, Consultant: Merck. S. Shell: Financial Interests, Personal, Full or part-time Employment: Guardant Health; Financial Interests, Personal, Stocks/Shares: Guardant Health. A. Yablonovitch: Financial Interests, Personal, Full or part-time Employment: Guardant Health; Financial Interests, Personal, Stocks/Shares: Guardant Health. G. Guezel: Financial Interests, Personal, Full or part-time Employment: Merck. J. Scheuenpflug: Financial Interests, Personal, Full or part-time Employment: Merck. All other authors have declared no conflicts of interest.

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Colorectal cancer

436TiP - COLSTAR: Randomized, open-label, multicentre, phase III study comparing futuximab/modotuximab plus trifluridine/tipiracil to trifluridine/tipiracil in KRAS/NRAS and BRAF wild type (wt) metastatic colorectal cancer (mCRC) previously treated with both standard and anti-EGFR treatment

Presentation Number
436TiP
Speakers
  • Fortunato Ciardiello (Napoli, Italy)
Date
Sun, 11.09.2022

Abstract

Background

Approved treatments for 3rd-line mCRC are limited and outcomes remain poor. Trifluridine/tipiracil (TT) is a standard of care option for patients previously treated/not considered candidates for available therapies. Futuximab/modotuximab (FuMo) is a biological composed of a 1:1 mixture of two monoclonal antibodies, futuximab and modotuximab, that bind to non-overlapping epitopes on the extracellular domain (ECD) of EGFR. FuMo has demonstrated activity in RAS/BRAF wt mCRC EGFR-pretreated patients in the Sym004-05 phase II study. Anti-EGFR Mabs have been safely combined with TT.

Trial design

COLSTAR (NCT05223673) is a randomized, open-label, phase III study comparing FuMo + TT with TT alone with a safety lead-in (SLI) part. Main eligibility criteria include KRAS/NRAS (exons 2, 3 and 4) and BRAF wt (V600E mutation) (double negative; DN) assessed by centralized analysis of ctDNA at screening, and previous treatment with at least 2 regimens including fluoropyrimidine, irinotecan, oxaliplatin, at least one anti-VEGF (bevacizumab, aflibercept, ramucirumab, regorafenib) and at least one anti-EGFR mAb (cetuximab or panitumumab) for ≥4 months. Randomization will be done in a 1:1 ratio to TT (35 mg/m2 BID on days 1-5 and days 8-12 of a 28-day cycle) or to the same dose of TT + FuMo (9 mg/kg loading dose on day 1 of cycle 1 followed by 6 mg/kg weekly). Stratification will be done according to performance status (ECOG 0 vs 1), previous regimens of treatment (2 vs ≥3), and EGFR ECD mutations (presence vs absence). Approximately 25 patients will be enrolled in the SLI part and 500 in the randomized part of the study. Primary objectives are: safety and tolerability of FuMo + TT according to CTCAE v5.0 (part 1) and superiority of the combination in terms of OS in the DN population (part 2). The key secondary endpoint is OS in the triple-negative (KRAS/NRAS, BRAF, and EGFR-ECD wt) population (part 2). A group sequential design with 3 interim analyses (IA) will allow to stop the trial prematurely for futility at each IA as well as for efficacy at last IA.

Clinical trial identification

NCT05223673.

Legal entity responsible for the study

Institut de Recherches Internationales Servier.

Funding

Institut de Recherches Internationales Servier.

Disclosure

F. Ciardiello: Financial Interests, Personal, Advisory Board: Roche, Merck Serono, Servier, Pierre Fabre, Pfizer; Financial Interests, Institutional, Research Grant: Merck Serono, Roche, Amgen; Financial Interests, Institutional, Invited Speaker: Pfizer, Pierre Fabre, Servier. T. Yoshino: Financial Interests, Personal, Invited Speaker: Chugai, Merck Biopharma, Bayer, Ono, MSD; Financial Interests, Institutional, Invited Speaker: Ono, Sanofi, Daiichi Sankyo, Chugai, Pfizer; Financial Interests, Institutional, Research Grant: Taiho, MSD, Ono, Amgen, Genomedia, Sysmex, Daiichi Sankyo, Chugai, Boehringer Ingelheim. D.P. Modest: Financial Interests, Personal, Principal Investigator: Servier; Financial Interests, Personal, Research Grant: Amgen, Servier; Financial Interests, Personal, Advisory Role: Servier, Amgen, Merck, G1, Transgene, BMS, MSD, Pierre Fabre, Onkowissen, Lilly, Sanofi, AstraZeneca; Financial Interests, Personal, Invited Speaker: Amgen, Servier, Merck, G1, Transgene, BMS, MSD, Pierre Fabre, Onkowissen, Lilly, Sanofi, AstraZeneca; Financial Interests, Personal, Other, Travel support: Amgen, Servier; Financial Interests, Personal, Advisory Board: G1. L. Martin Fernandez: Financial Interests, Personal, Full or part-time Employment: Servier. L. ROBY: Financial Interests, Personal, Full or part-time Employment: Servier. R. Fougeray: Financial Interests, Personal, Full or part-time Employment: Servier. B.P. Lockhart: Financial Interests, Personal, Full or part-time Employment: Servier. J. Tabernero: Financial Interests, Personal, Advisory Board, scientific consultancy role: Orion Biotechnology, Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daichii Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics, TheraMyc, Hutchinson MediPharma International, Avvinity, Scandion Oncology, Ona Therapeutics, Sotio Biotech, Inspirna Inc; Financial Interests, Personal, Invited Speaker, educational collaboration: Medscape Education, Physicians Education Resource (PER), PeerView Institute for Medical Education, Imedex; Financial Interests, Personal, Invited Speaker, educacional collaboration: MJH Life Sciences; Financial Interests, Institutional, Research Grant, ACRCelerate: Colorectal Cancer Stratified: Fundación Científica de la Asociación Española Contra el Cáncer; Financial Interests, Institutional, Research Grant, OPTIMISTICC: Opportunity to Investigate the Microbiome’s Impact on Science and Treatment In Colorectal Cancer: Cancer Research UK; Financial Interests, Institutional, Funding, Clinical Trials & Research: Amgen Inc, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb International Corporation, Genentech Inc, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Janssen-Cilag International NV, Merck Health KGAA, Merck, Sharp & Dohme de España, SA, Novartis Farmacéutica SA, PharmaMar SA, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA, Inc, BeiGene, Boehringer Ingelheim, HalioDX SAS, Hutchinson Medipharma, Pfizer, MedImmune, Menarini, Merus N V, Mirati; Non-Financial Interests, Invited Speaker, Board of Directors: Cancer Core Europe, Spanish Association Against Cancer -AECC; Non-Financial Interests, Invited Speaker, General Assembly: Horizon Europe Cancer Mission; Non-Financial Interests, Advisory Role, Scientific Advisory Board: Karolinska Comprehensive Cancer Centre; Non-Financial Interests, Leadership Role, External Scientific Committee: Institute for Health Research INCLIVA – Clinical Hospital of Valencia, IdiSNA –Universidad de Navarra; Non-Financial Interests, Leadership Role, Scientific Advisory Board: Spanish National Cancer Research Centre (CNIO); Non-Financial Interests, Advisory Role, International Scientific Evaluation Committee: Bosch Health Campus (BHC); Non-Financial Interests, Advisory Role, Review Board: National Decade Against Cancer (NCT) - German Consortium for Translational Cancer Research (DKTK); Non-Financial Interests, Advisory Role, International Review Committee (IRC): Oncode Institute; Non-Financial Interests, Advisory Role, Scientific Advisory Board (SAB): Oslo University Hospital Comprehensive Cancer Centre (OUH CCC); Non-Financial Interests, Leadership Role, Governance Advisory Committee: European Organization for Research and Treatment of Cancer -EORTC; Non-Financial Interests, Principal Investigator, Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutics LP, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, MedImmune, Menarini, Merck Healthcare KGAA, Merck, Sharp & Dohme de España SA, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc; Non-Financial Interests, Leadership Role, Vice Chairman: World Innovative Networking (WIN) Consortium in Personalized Cancer Medicine; Non-Financial Interests, Other, Coordinating PI & Steering Committee Member. Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutical LP, Boehringer Ingelheim, MedImmune, Menarini, Merck Healthcare KGAA, Merck, Sharp & Dohme de España SA, Pfizer, Servier; Non-Financial Interests, Other, Steering Committee Member. Clinical Trials & Research: Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc., Hutchinson Medipharma, HalioDX SAS, Janssen-Cilag International NV, Merus NV, Taiho Pharma USA Inc; Non-Financial Interests, Other, Coordinating PI. Clinical Trials & Research: Mirati; Non-Financial Interests, Member: AACR, ASCO, EACR, EORTC, SEOM; Other, Other, President: Oncology Master Plan – Catalonia Department of Health; Other, Other, Advisory Committee: Advisory Committee on Pharmaceutical Provision Financing under the Spanish National Health System.

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Breast cancer, early stage

182P - Trends and variations of endocrine treatment in "in situ” breast cancer in Europe

Presentation Number
182P
Speakers
  • Lien Van Walle (Brussels, Belgium)
Date
Sat, 10.09.2022

Abstract

Background

Quality indicators (QI) are a specific tool to measure the quality of provided care. QI must be reliable, relevant, interpretable, actionable, and measurable. Contrarily to invasive breast cancer (IBC), the management of in situ breast cancer (BCIS) with adjuvant endocrine treatment (ET) remains controversial. The study aims to investigate the use of adjuvant ET in breast cancer in European (EU) countries, employing the European Society of Breast Cancer Specialists (EUSOMA) database that contains data collected by EU breast centers, that in the relevant time period were part of the EUSOMA Network.

Methods

We identified all females with a new breast cancer diagnosed in the period 2010 to 2019 in the EUSOMA database. The analysis was conducted on anonymous and cumulative data. The data were registered by 58 EU breast centers, all of which entered at least 500 new diagnoses in the database in the ten-year period. Geographically, the contributing centers are located in Northern (Belgium, the Netherlands, Sweden), Central (Austria, France, Germany, Switzerland) and Southern (Italy, Portugal) EU. The use of ET by tumor behavior was studied in operated endocrine sensitive breast cancer. Trends were evaluated by age group (<50y, 50-69y, ≥70y) and geographical region (North, Central, South).

Results

A total of 77,835 operated patients with endocrine sensitive breast cancer was included, 72,749 IBC and 5,086 BCIS. In IBC, adjuvant ET was systematically given (94%) and in all age groups at least in 90%. Geographically, proportions were slightly higher in Southern EU breast centers (97%) compared to both Northern and Central EU (91%). In BCIS, 46% of endocrine sensitive patients received adjuvant ET. In patients older than 70 less adjuvant ET was used (38%) compared with the younger patients. Geographically, the same gradient as for IBC was observed: higher proportions in Southern EU breast centers (52%) compared to both Northern and Central EU (40%).

Conclusions

The study of the real-world use of adjuvant ET in BCIS revealed a remarkably high percentage. Geographical study between EU centers and regions demonstrated different practices. QI making use of real-world EU data can help to monitor, evaluate, and eventually guide and align good clinical practice in the management of BC.

Editorial acknowledgement

EUSOMA Working Group: Bettina Ballardini,Centro di Senologia Gruppo MultiMedica, Ospedale San Giuseppe, Ospedale MultiMedica Castellanza, IRCCS MultiMedica, Italy. Elisabetta Benozzi,Centro di Riferimento Oncologico di Aviano, Italy. Johannes Berger, Elisabethinen Hospital Linz, Austria. Martine Berlière, Clinique du Sein Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Bruxelles, Belgium. Renzo Boldorini, AOU Maggiore della Carità e CPO -SSD Epidemiologia dei Tumori, Novara, Italy. Andrea Bonetti, Breast Centre Azienda Ulss9 Scaligera, Legnago, Italy. Marina Bortul, Breast Centre Azienda Sanitaria Universitaria Integrata di Trieste, Italy. Barbara Bussels, Radiotherapie, Gastro-intestinale oncologie en senologie, AZ Delta Roeselare, Belgium. Katia Cagossi, Breast Centre AUSL Modena Carpi, Italy. Maria João Cardoso, Breast Unit, Champalimaud Clinical Center/Champalimaud Foundation, Lisbon, Portugal. Birgit Carly, Breast Unit and Prevention Center Isala, Department Gynecology-Obstetrics, CHU St. Pierre, Brussels, Belgium. Francesco Caruso, Breast Centre Humanitas Catania, Humanitas Istituto Clinico Catanese S.p.A., Misterbianco, Catania, Italy. Carla Cedolini, Chirurgia Senologica, Dipartimento di Chirurgia Generale, Azienda Sanitaria Universitaria Integrata di Udine, Italy. Fabio Corsi, Breast Unit, Department of Surgery, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy and Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Milan, Milan, Italy. Elisabetta Cretella, Oncologia Medica, Ospedale di Bolzano, Azienda Sanitaria Alto Adige, Italy. Evelyn Despierre, Breast Clinic – Department of Gynaecology and Obstetrics, OLV-ziekenhuis, Aalst, Belgium. Luca Despini, Breast Surgery Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy. Rudy Leon De Wilde, University Hospital für Gynecology, Pius Hospital, Carl von Ossietzky University, Oldenburg, Germany. Antonio Esgueva, Clinica Universidad de Navarra, Regional multicentre, Madrid, Spain. Gianluca Fogazzi, Medical Oncology, Istituto Clinico S.Anna – Brescia, Italy. Lucio Fortunato, Chirurgia Senologica,UOC Centro di Senologia, Azienda Ospedaliera San Giovanni Addolorata, Roma, Italy. José Luis Fougo, Breast Centre, Centro Hospitalar Universitário São João, Porto, Portugal. Kay Friedrichs, Mammazentrum Hamburg am Krankenhaus Jerusalem, Hamburg, Germany. Daniele Generali, Azienda Socio Sanitaria Territoriale di Cremona, Italy. Simona GrossiCentro Senologico Specialistico Asl Lanciano-Vasto-Chieti, Ortona, Italy. Alessandra Huscher, Centro Senologico Multidisciplinare Fondazione Poliambulanza, Brescia, Italy. Michalis Kailides, Nicosia Breast Centre, Nicosia, Cyprus. Christelle Levy, Institut Norman du Sein, Centre François Baclesse, Caen, France. Sophie Marquette, Jessa Ziekenhuis - Hasselt – Belgium. Francesco Meani, Centro di Senologia Svizzera Italiana, Ginecologia e Ostetricia OR Lugano, Switzerland. Lorenzo Menghini, Breast Centre Ospedale Infermi di Rimini, Italy. Stefania Montemezzi, Centro Hub di Senologia Azienda Ospedaliera Universitaria Integrata Verona, Italy. Antonino Musolino, Department of Medicine and Surgery, University of Parma, Italy and Medical Oncology and Breast Unit, University Hospital of Parma, Italy. Ida Negreiros, UDTI and Lisbon Breast Unit, CUF Oncology, CUF, S.A. Lisbon, Portugal. Roger Olofsson Bagge, Sahlgrenska Breast Center, Sahlgrenska University Hospital, Gothenburg, Sweden. Gianmatteo Pagani, Breast Centre, Istituto Europeo di Oncologia, Milano Italy. Ana Car Peterko, Department of General Surgery and Surgical Oncology, Clinical Hospital Centre Rijeka, Rijeka, Croatia. Annemie Prové, Medische Oncologie, GZA Ziekenhuizen, Oncologisch Centrum. Wilrijk, Belgium. Manuela Roncella, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy. Gianni Saguatti, Breast Centre AUSL di Bologna -Azienda USL di Bologna - IRCCS Scienze Neurologiche, Bologna, Italy. Dimitri Sarlos, KSA Aarau Kantosspital, Aarau, Switzerland. Adele Sgarella, Breast Centre, Unità Operativa Complessa di Chirurgia Generale 3 Senologica e dei tessuti molli, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Gracienne Staelens, AZ Groeninge, Kortrijk, Belgium. Mario Taffurelli, IRCCS Azienda Ospedaliero-Universitaria di Bologna-Policlinico di Sant’Orsola, Bologna, Italy. Giovanni Tazzioli, Breast Unit Azienda Ospedaliero-Universitaria Policlinico Modena Italy. Corrado Tinterri, Humanitas Research Hospital Rozzano, Milan, Italy. Hans Torrenga, Deventer Ziekenhuis Hospital, Deventer, The Netherlands.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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