Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): a randomised, open-label, multicentre, phase 3 trial.

BACKGROUND

In advanced oestrogen receptor-positive, HER2-negative breast cancer, acquired resistance to aromatase inhibitors frequently stems from ESR1-mutated subclones, which might be sensitive to fulvestrant. The PADA-1 trial aimed to show the efficacy of an early change in therapy on the basis of a rising ESR1 mutation in blood (bESR1

METHODS

We did a randomised, open-label, phase 3 trial in 83 hospitals in France. Women aged at least 18 years with oestrogen receptor-positive, HER2-negative advanced breast cancer and an Eastern Cooperative Oncology Group performance status of 0-2 were recruited and monitored for rising bESR1

FINDINGS

From March 22, 2017, to Jan 31, 2019, 1017 patients were included, of whom 279 (27%) developed a rising bESR1

INTERPRETATION

PADA-1 is the first prospective randomised trial showing that the early therapeutic targeting of bESR1

FUNDING

Pfizer.

Informations de copyright

Copyright © 2022 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests F-CB reports, outside the submitted work, grants or contracts from Novartis, Lilly, Amgen, Sanofi, Radius, Seagen, AstraZeneca, General Electric, Menarini/Stemline, Menarini Silicon Biosystems, Merck, Pfizer, Prolynx, Rain Therapeutics, and Roche; consulting fees from AstraZeneca, Exact Sciences, General Electric, GlaxoSmithKline, Lilly, Menarini/Stemline, Novartis, Pfizer, Rain Therapeutics, and Sanofi; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Lilly, Menarini/Stemline, Pfizer, Rain Therapeutics, and Sanofi; support for attending meetings or travel from AstraZeneca, Pfizer, Novartis, and Roche; and applied for an international patent (application number PCT/EP2019/056445), filed on March 14, 2019, named: method for identifying one or more mutations in a hotspot mutation sequence. A-CH-B reports, outside the submitted work, consulting fees from AstraZeneca and Merck Sharpe & Dohme; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from MSD, AstraZeneca, Daiichi, GSK, Seagen, and Gilead; support for attending meetings or travel from Novartis, Pfizer, and Daiichi; and participation on a data safety monitoring board or advisory board for MSD, AstraZeneca, Daiichi, Pfizer, Novartis, GSK, Seagen, Gilead, and Eisai. TB reports, outside the submitted work, grants or contracts from Roche, AstraZeneca, Pfizer, and SeaGen; and consulting fees from AstraZeneca, Daiichi, Lilly, SeaGen, Roche, Novartis, and Pfizer. J-YP reports, outside the submitted work, grants or contracts from Servier and Menarini; consulting fees from Pfizer, Daiichi Sankyo, AstraZeneca, and MSD; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Daiichi Sankyo, Gilead, MSD, Seagen, Novartis, Lilly, Pierre Fabre, and Amgen; support for attending meetings or travel from Roche and AstraZeneca; and participation on a data safety monitoring board or advisory board for Sanofi and Novartis. TdlMR reports, outside the submitted work, grants or contracts from Novartis, Pfizer, AstraZeneca, MSD, Roche, Pfizer, and Seagen; consulting fees from AstraZeneca, Clovis Oncology, Eisai, MSD, Novartis, Pfizer, Roche, Sanofi, Tesaro, GSK, and Seagen; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from GSK. RS reports, outside the submitted work, grants or contracts from AstraZeneca; consulting fees from GSK; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Novartis, GSK, Clovis, and AstraZeneca; and support for attending meetings or travel from Pfizer, Roche, GSK, and Bristol Myers Squibb. J-SF reports, outside the submitted work, consulting fees from Pfizer, Lilly, Novartis, AstraZeneca, Clovis Oncology, GSK, Gilead, Daiichi Sankyo, and Seagen; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Lilly, Novartis, AstraZeneca, Gilead, Daiichi Sankyo, and Seagen; and support for attending meetings or travel from Pfizer, Lilly, Novartis, AstraZeneca, Clovis Oncology, GSK, Gilead, Daiichi Sankyo, and Seagen. SL reports, outside the submitted work, grants or contracts from Novartis, Eisai, and BMS; consulting fees from Pfizer, Novartis, Lilly, AstraZeneca, Sanofi, Astellas, Janssen, Ipsen, Roche, BMS, Daiichi, Seagen, and Pierre Fabre; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Pfizer, Novartis, Lilly, AstraZeneca, Sanofi, Astellas, Janssen, Ipsen, Roche, BMS, Daiichi, Seagen, and Pierre Fabre; payment for expert testimony from Pfizer, Novartis, Lilly, AstraZeneca, Sanofi, Astellas, Janssen, Ipsen, Roche, BMS, Daiichi, and Seagen; support for attending meetings or travel from Pfizer, Novartis, AstraZeneca, Janssen, BMS, Daiichi, and Seagen; and receipt of equipment, materials, drugs, medical writing, gifts, or other services from BMS. CL reports, outside the submitted work, consulting fees from MSD, Daiichi, Roche, and AstraZeneca; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Lilly; support for attending meetings or travel from Roche, Pfizer, Sandoz, Lilly, and AstraZeneca; and participation on a data safety monitoring board or advisory board for Roche, AstraZeneca, and Lilly. AL reports, outside the submitted work, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, MSD, and Clovis; participation on a data safety monitoring board or advisory board for AstraZeneca, MSD, and Clovis; and leadership or fiduciary role in other board for GINECO group. JG reports, outside the submitted work, support for attending meetings or travel from Lilly and Daiichi; and participation on a data safety monitoring board or advisory board for Daiichi and Pfizer. HV reports, outside the submitted work, grants or contracts from Eisai, Novartis, AstraZeneca, Daiichi, and Pfizer; and support for attending meetings or travel from Eisai, GSK, MSD, and Novartis. CG-T reports, outside the submitted work, grants or contracts from Pfizer; consulting fees from Pfizer; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Astrazeneca, Pfizer and Novartis; and support for attending meetings or travel from MSD, Mylan, and Pfizer. BP reports, outside the submitted work, consulting fees from AstraZeneca, Myriad, Pierre Fabre, and Pfizer; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Daiichi Sankyo, Novartis, and Puma; support for attending meetings or travel from AstraZeneca, Pierre Fabre, and MSD; and participation on a data safety monitoring board or advisory board for Novartis, AstraZeneca, and Daiichi Sankyo. FA reports, outside the submitted work, reports grants or contracts from Roche, AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, and Lilly; and consulting fees from Gilead, Guardant Health, MedImmune, and Relay Therapeutics. LA reports, outside the submitted work, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Roche, MSD, AstraZeneca, and BMS; and support for attending meetings or travel from Roche. JL reports a Pfizer grant to his institution for carrying out this study. SD reports, outside the submitted work, grants or contracts from AstraZeneca, Pfizer, Novartis, Roche Genentech, Lilly, Puma, Myriad, Orion, Amgen, Sanofi, MSD, BMS, Seagen, and Taiho; consulting fees from Isis/Servier, Cellectis, Pierre Fabre, and General Electric; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Seagen, AstraZeneca, Pfizer, Exact Sciences, Daiichi, and Lilly; support for attending meetings or travel from Pfizer, AstraZeneca, and Roche Genentech; and participation on a data safety monitoring board or advisory board for AstraZeneca, Sanofi, Orion, and Rappta. All other authors declare no competing interests.