Long-term outcomes in patients with PET-predicted poor-responsive HER2-positive breast cancer treated with neoadjuvant bevacizumab added to trastuzumab and docetaxel: 5-year follow-up of the randomised Avataxher study
Background: The open-label, randomised Phase 2 AVATAXHER study (NCT01142778) demonstrated that early PET assessment identified HER2-positive breast cancer patients who responded poorly to neoadjuvant docetaxel plus trastuzumab. Adding neoadjuvant bevacizumab for PET-predicted poor-responders improve...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-11-01
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| Series: | EClinicalMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537020303102 |
| _version_ | 1819327268799905792 |
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| author | Bruno Coudert Jean-Yves Pierga Marie-Ange Mouret-Reynier Kaldoun Kerrou Jean-Marc Ferrero Thierry Petit Fanny Le Du Pierre-François Dupré Thomas Bachelot Philippe Gabelle Marie-Pierre Chauvet David Coeffic Catherine Barbe Jean-Briac Prevost Gilles Paintaud Gilles Thibault Abdennour Ferhat Julien Dupin Alina Berriolo-Riedinger Laurent Arnould |
| author_facet | Bruno Coudert Jean-Yves Pierga Marie-Ange Mouret-Reynier Kaldoun Kerrou Jean-Marc Ferrero Thierry Petit Fanny Le Du Pierre-François Dupré Thomas Bachelot Philippe Gabelle Marie-Pierre Chauvet David Coeffic Catherine Barbe Jean-Briac Prevost Gilles Paintaud Gilles Thibault Abdennour Ferhat Julien Dupin Alina Berriolo-Riedinger Laurent Arnould |
| author_sort | Bruno Coudert |
| collection | DOAJ |
| description | Background: The open-label, randomised Phase 2 AVATAXHER study (NCT01142778) demonstrated that early PET assessment identified HER2-positive breast cancer patients who responded poorly to neoadjuvant docetaxel plus trastuzumab. Adding neoadjuvant bevacizumab for PET-predicted poor-responders improved pathological complete response (pCR) rates (43.8% vs 24.0%). We investigated long-term study outcomes. Methods: Patients were treated in three groups. All patients initially received two cycles of standard neoadjuvant therapy with [¹⁸F]-FDG PET conducted before each cycle. Those with ≥70% change in the maximum standardised uptake value (∆SUVmax) received four further cycles of standard neoadjuvant therapy (PET responders). PET-predicted poor-responders (∆SUVmax <70%) were randomised (2:1) to neoadjuvant therapy with (Group A) or without (Group B) bevacizumab for cycles 3–6. All patients received one further cycle of trastuzumab before surgery plus adjuvant trastuzumab (11 cycles). Findings: 142 patients were randomized and treated (PET responders, n = 69; Group A, n = 48; Group B, n = 25). 5-year disease-free survival rates were 90.5% (95% CI: 80.0–95.6%) in PET responders, 90.2% (95% CI: 75.9–96.2%) in Group A, and 76.0% (95% CI: 54.2–88.4%) in Group B. However, no difference was observed between randomised arms in a sensitivity analysis. During adjuvant therapy, the incidence of Grade ≥3 (Group A: 25.6%; Group B 12.5%) and serious adverse events (Group A: 18.6%; Group B 12.5%) was higher in Group A vs Group B, but with no apparent effect on cardiac events. Interpretation: In patients with HER2-positive breast cancer, an intervention based on early PET assessment and improvement of pCR does not modify disease-free survival. Funding: Roche France. |
| first_indexed | 2024-12-24T13:08:09Z |
| format | Article |
| id | doaj.art-e12828e210e34b18a595bb3ec526544b |
| institution | Directory Open Access Journal |
| issn | 2589-5370 |
| language | English |
| last_indexed | 2024-12-24T13:08:09Z |
| publishDate | 2020-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj.art-e12828e210e34b18a595bb3ec526544b2022-12-21T16:53:57ZengElsevierEClinicalMedicine2589-53702020-11-0128100566Long-term outcomes in patients with PET-predicted poor-responsive HER2-positive breast cancer treated with neoadjuvant bevacizumab added to trastuzumab and docetaxel: 5-year follow-up of the randomised Avataxher studyBruno Coudert0Jean-Yves Pierga1Marie-Ange Mouret-Reynier2Kaldoun Kerrou3Jean-Marc Ferrero4Thierry Petit5Fanny Le Du6Pierre-François Dupré7Thomas Bachelot8Philippe Gabelle9Marie-Pierre Chauvet10David Coeffic11Catherine Barbe12Jean-Briac Prevost13Gilles Paintaud14Gilles Thibault15Abdennour Ferhat16Julien Dupin17Alina Berriolo-Riedinger18Laurent Arnould19Centre Georges-Francois Leclerc, Dijon, France; Corresponding author.Institut Curie, Université de Paris, Paris, FranceCentre Jean Perrin, Clermont Ferrand, FranceHopital Tenon, Paris, FranceCentre Antoine Lacassagne, Nice, FranceCentre Paul Strauss, Strasbourg, FranceCentre Eugène Marquis, Rennes, FranceCentre Hospitalier Universitaire Augustin-Morvan, Brest, FranceCentre Léon Berard, Lyon, FranceInstitut Daniel Hollard, Grenoble, FranceCentre Oscar Lambret, Lille, FrancePolyclinique Courlancy, Institut du Cancer Courlancy Reims, FranceCHU Bretonneau, Tours, FranceCentre Pierre Curie, Beuvry, FranceUniversité de Tours, CHRU de Tours, Tours, FranceUniversité de Tours, CHRU de Tours, Tours, FranceRoche France S.A.S., Boulogne Billancourt, FranceRoche France S.A.S., Boulogne Billancourt, FranceCentre Georges-Francois Leclerc, Dijon, FranceCentre Georges-Francois Leclerc, Dijon, FranceBackground: The open-label, randomised Phase 2 AVATAXHER study (NCT01142778) demonstrated that early PET assessment identified HER2-positive breast cancer patients who responded poorly to neoadjuvant docetaxel plus trastuzumab. Adding neoadjuvant bevacizumab for PET-predicted poor-responders improved pathological complete response (pCR) rates (43.8% vs 24.0%). We investigated long-term study outcomes. Methods: Patients were treated in three groups. All patients initially received two cycles of standard neoadjuvant therapy with [¹⁸F]-FDG PET conducted before each cycle. Those with ≥70% change in the maximum standardised uptake value (∆SUVmax) received four further cycles of standard neoadjuvant therapy (PET responders). PET-predicted poor-responders (∆SUVmax <70%) were randomised (2:1) to neoadjuvant therapy with (Group A) or without (Group B) bevacizumab for cycles 3–6. All patients received one further cycle of trastuzumab before surgery plus adjuvant trastuzumab (11 cycles). Findings: 142 patients were randomized and treated (PET responders, n = 69; Group A, n = 48; Group B, n = 25). 5-year disease-free survival rates were 90.5% (95% CI: 80.0–95.6%) in PET responders, 90.2% (95% CI: 75.9–96.2%) in Group A, and 76.0% (95% CI: 54.2–88.4%) in Group B. However, no difference was observed between randomised arms in a sensitivity analysis. During adjuvant therapy, the incidence of Grade ≥3 (Group A: 25.6%; Group B 12.5%) and serious adverse events (Group A: 18.6%; Group B 12.5%) was higher in Group A vs Group B, but with no apparent effect on cardiac events. Interpretation: In patients with HER2-positive breast cancer, an intervention based on early PET assessment and improvement of pCR does not modify disease-free survival. Funding: Roche France.http://www.sciencedirect.com/science/article/pii/S2589537020303102Her-2 positive breast cancerBevacizumabNeoadjuvantPositron emission tomographyEarly pet assessmentΔsuvmax |
| spellingShingle | Bruno Coudert Jean-Yves Pierga Marie-Ange Mouret-Reynier Kaldoun Kerrou Jean-Marc Ferrero Thierry Petit Fanny Le Du Pierre-François Dupré Thomas Bachelot Philippe Gabelle Marie-Pierre Chauvet David Coeffic Catherine Barbe Jean-Briac Prevost Gilles Paintaud Gilles Thibault Abdennour Ferhat Julien Dupin Alina Berriolo-Riedinger Laurent Arnould Long-term outcomes in patients with PET-predicted poor-responsive HER2-positive breast cancer treated with neoadjuvant bevacizumab added to trastuzumab and docetaxel: 5-year follow-up of the randomised Avataxher study EClinicalMedicine Her-2 positive breast cancer Bevacizumab Neoadjuvant Positron emission tomography Early pet assessment Δsuvmax |
| title | Long-term outcomes in patients with PET-predicted poor-responsive HER2-positive breast cancer treated with neoadjuvant bevacizumab added to trastuzumab and docetaxel: 5-year follow-up of the randomised Avataxher study |
| title_full | Long-term outcomes in patients with PET-predicted poor-responsive HER2-positive breast cancer treated with neoadjuvant bevacizumab added to trastuzumab and docetaxel: 5-year follow-up of the randomised Avataxher study |
| title_fullStr | Long-term outcomes in patients with PET-predicted poor-responsive HER2-positive breast cancer treated with neoadjuvant bevacizumab added to trastuzumab and docetaxel: 5-year follow-up of the randomised Avataxher study |
| title_full_unstemmed | Long-term outcomes in patients with PET-predicted poor-responsive HER2-positive breast cancer treated with neoadjuvant bevacizumab added to trastuzumab and docetaxel: 5-year follow-up of the randomised Avataxher study |
| title_short | Long-term outcomes in patients with PET-predicted poor-responsive HER2-positive breast cancer treated with neoadjuvant bevacizumab added to trastuzumab and docetaxel: 5-year follow-up of the randomised Avataxher study |
| title_sort | long term outcomes in patients with pet predicted poor responsive her2 positive breast cancer treated with neoadjuvant bevacizumab added to trastuzumab and docetaxel 5 year follow up of the randomised avataxher study |
| topic | Her-2 positive breast cancer Bevacizumab Neoadjuvant Positron emission tomography Early pet assessment Δsuvmax |
| url | http://www.sciencedirect.com/science/article/pii/S2589537020303102 |
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