1. Real-Time Detection of ESR1 Mutation in Blood by Droplet Digital PCR in the PADA-1 Trial: Feasibility and Cross-Validation with NGS
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Celine Callens, Francois-Clement Bidard, Anaïs Curto-Taribo, Olfa Trabelsi-Grati, Samia Melaabi, Suzette Delaloge, Anne-Claire Hardy-Bessard, Thomas Bachelot, Florian Clatot, Thibault De La Motte Rouge, Jean-Luc Canon, Laurent Arnould, Fabrice Andre, Sandrine Marques, Marc-Henri Stern, Jean-Yves Pierga, Anne Vincent-Salomon, Camille Benoist, Emmanuelle Jeannot, Frederique Berger, Ivan Bieche, Anne Pradines, Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Armoricain de Radiothérapie, d'Imagerie médicale et d'Oncologie [Plérin, Saint-Brieuc] (CARIO), Centre Léon Bérard [Lyon], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Eugène Marquis (CRLCC), Département de Biologie et pathologie des tumeurs [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, UNICANCER, Unité de génétique et biologie des cancers (U830), Université Paris Cité - UFR Médecine Paris Centre [Santé] (UPC Médecine Paris Centre), Université Paris Cité (UPC), Institut Curie [Paris], Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Claudius Regaud, Pfizer, AstraZeneca, Roche, Ministère des Affaires Sociales et de la Santé, Institut National Du Cancer, INCa: PRT-K19-110, Institut Curie: INCa-DGOS-INSERM_12554, The authors declare the following competing financial interest(s): F.-C.B.: Grants from Pfizer during the conduct of the study, grants, personal fees, and nonfinancial support from Pfizer and Novartis personal fees from Lilly, Amgen, Sanofi, and Radius personal fees and nonfinancial support from Roche and AstraZeneca, grants and personal fees from Seagen, and grants from Prolynx outside the submitted work, and a pending patent on ctDNA detection by ddPCR. F.-C.B., M.-H.S., and E.J. are coholders of a patent related to ESR1 mutation detection (PCT/EP2019/056445). S.D.: Consulting Fees (e.g., advisory boards), Author, AstraZeneca, Besins, Rappta. Contracted Research, Pfizer, MSD, BMS, AstraZeneca, Orion, Sanofi, Novartis, Puma, Roche, Lilly, Daich. A.-C.H.-B.: Personal fees from AstraZeneca, Daiichi, Clovis, GSK, MSD, Novartis, Pfizer, and Roche outside the submitted work. T.B.: Consulting Fees (e.g., advisory boards), AstraZeneca, SeaGen, Roche, Novartis, Pfizer. Contracted Research, Roche, AstraZeneca, Pfizer, SeaGen. T.D.L.M.R.: Consulting Fees (e.g., advisory boards), AstraZeneca, Clovis Oncology, Eisai, MSD, Novartis, Pfizer, Roche, Sanofi, Tesaro. Contracted Research, Novartis, Pfizer, AstraZeneca. Other, AstraZeneca, MSD, Roche, Pfizer. F.A.: Grants from Roche, AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, and Lilly outside the submitted work. M.S.: Receipt of Intellectual Property Rights/Patent Holder, patent on ESR1 ddPCR. J.P.: Consulting Fees (e.g., advisory boards), Exact Sciences, AstraZeneca, Daiichi, Sankyo, Lilly, Novartis, Pfizer, Pierre Fabre, Oncology, Roche, SeaGen. Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speaker bureaus), Amgen, MSD, Novartis, Pfizer, SeaGen. Contracted Research, Servier, Roche. F.J.: Receipt of Intellectual Property Rights/Patent Holder, patent on ESR1 ddPCR. Acknowledgments, and This study was supported by a grant from the French Ministry of Health and the French National Cancer Institute (Grant PRT-K19-110) and Pfizer. The PADA-1 trial was funded by Pfizer through a grant to Unicancer. The initial development of the bESR1 assay used in the trial was supported by the Institut Curie SIRIC2 program (Grant INCa-DGOS-INSERM_12554). mut
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[CHIM.ANAL]Chemical Sciences/Analytical chemistry ,Mutation ,Feasibility Studies ,High-Throughput Nucleotide Sequencing ,Humans ,Polymerase Chain Reaction ,Circulating Tumor DNA ,Analytical Chemistry - Abstract
International audience; The clinical actionability of circulating tumor DNA requires sensitive detection methods with a short turnaround time. In the PADA-1 phase 3 trial (NCT03079011), metastatic breast cancer patients treated with an aromatase inhibitor and palbociclib were screened every 2 months for activating ESR1 mutations in blood (bESR1mut). We report the feasibility of the droplet digital polymerase chain reaction (ddPCR) and cross-validation with next-generation sequencing (NGS). bESR1mut testing was centralized in two platforms using the same ddPCR assay. Results were reported as copies/mL of plasma and mutant allele frequency (MAF). We analyzed 200 positive ddPCR samples with an NGS assay (0.5-1% sensitivity). Overall, 12,552 blood samples were collected from 1017 patients from 83 centers. Among the 12,525 available samples with ddPCR results, 11,533 (92%) were bESR1mut-negative. A total of 267 patients newly displayed bESR1mut (26% patients/2% samples) with a median copy number of 14/mL (range: 4-1225) and a median MAF of 0.83% (0.11-35), 648 samples (20% patients/5% samples) displayed persistent bESR1mut, and 77 (
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- 2022