3-year invasive disease-free survival with chemotherapy de-escalation using an 18F-FDG-PET-based, pathological complete response-adapted strategy in HER2-positive early breast cancer (PHERGain): a randomised, open-label, phase 2 trial.
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| Title: | 3-year invasive disease-free survival with chemotherapy de-escalation using an 18F-FDG-PET-based, pathological complete response-adapted strategy in HER2-positive early breast cancer (PHERGain): a randomised, open-label, phase 2 trial. |
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| Authors: | Pérez-García, José Manuel (AUTHOR), Cortés, Javier (AUTHOR), Ruiz-Borrego, Manuel (AUTHOR), Colleoni, Marco (AUTHOR), Stradella, Agostina (AUTHOR), Bermejo, Begoña (AUTHOR), Dalenc, Florence (AUTHOR), Escrivá-de-Romaní, Santiago (AUTHOR), Calvo Martínez, Lourdes (AUTHOR), Ribelles, Nuria (AUTHOR), Marmé, Frederik (AUTHOR), Cortés, Alfonso (AUTHOR), Albacar, Cinta (AUTHOR), Gebhart, Geraldine (AUTHOR), Prat, Aleix (AUTHOR), Kerrou, Khaldoun (AUTHOR), Schmid, Peter (AUTHOR), Braga, Sofia (AUTHOR), Di Cosimo, Serena (AUTHOR), Gion, Maria (AUTHOR) |
| Source: | Lancet. 4/27/2024, Vol. 403 Issue 10437, p1649-1659. 11p. |
| Subjects: | F. Hoffmann-La Roche Ltd., Hormone receptor positive breast cancer, HER2 positive breast cancer, Epidermal growth factor receptors, Progression-free survival |
| Abstract: | PHERGain was designed to assess the feasibility, safety, and efficacy of a chemotherapy-free treatment based on a dual human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab and pertuzumab in patients with HER2-positive early breast cancer (EBC). It used an 18fluorine-fluorodeoxyglucose-PET-based, pathological complete response (pCR)-adapted strategy. PHERGain was a randomised, open-label, phase 2 trial that took place in 45 hospitals in seven European countries. It randomly allocated patients in a 1:4 ratio with centrally confirmed, HER2-positive, stage I–IIIA invasive, operable breast cancer with at least one PET-evaluable lesion to either group A, where patients received docetaxel (75 mg/m2, intravenous), carboplatin (area under the curve 6 mg/mL per min, intravenous), trastuzumab (600 mg fixed dose, subcutaneous), and pertuzumab (840 mg loading dose followed by 420 mg maintenance doses, intravenous; TCHP), or group B, where patients received trastuzumab and pertuzumab with or without endocrine therapy, every 3 weeks. Random allocation was stratified by hormone receptor status. Centrally reviewed PET was conducted at baseline and after two treatment cycles. Patients in group B were treated according to on-treatment PET results. Patients in group B who were PET-responders continued with trastuzumab and pertuzumab with or without endocrine therapy for six cycles, while PET-non-responders were switched to receive six cycles of TCHP. After surgery, patients in group B who were PET-responders who did not achieve a pCR received six cycles of TCHP, and all patients completed up to 18 cycles of trastuzumab and pertuzumab. The primary endpoints were pCR in patients who were group B PET-responders after two treatment cycles (the results for which have been reported previously) and 3-year invasive disease-free survival (iDFS) in patients in group B. The study is registered with ClinicalTrials.gov (NCT03161353) and is ongoing. Between June 26, 2017, and April 24, 2019, a total of 356 patients were randomly allocated (71 patients in group A and 285 patients in group B), and 63 (89%) and 267 (94%) patients proceeded to surgery in groups A and B, respectively. At this second analysis (data cutoff: Nov 4, 2022), the median duration of follow-up was 43·3 months (range 0·0–63·0). In group B, the 3-year iDFS rate was 94·8% (95% CI 91·4–97·1; p=0·001), meeting the primary endpoint. No new safety signals were identified. Treatment-related adverse events and serious adverse events (SAEs) were numerically higher in patients allocated to group A than to group B (grade ≥3 62% vs 33%; SAEs 28% vs 14%). Group B PET-responders with pCR presented the lowest incidence of treatment-related grade 3 or higher adverse events (1%) without any SAEs. Among HER2-positive EBC patients, a PET-based, pCR-adapted strategy was associated with an excellent 3-year iDFS. This strategy identified about a third of patients who had HER2-positive EBC who could safely omit chemotherapy. F Hoffmann-La Roche. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 176925441 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: 3-year invasive disease-free survival with chemotherapy de-escalation using an 18F-FDG-PET-based, pathological complete response-adapted strategy in HER2-positive early breast cancer (PHERGain): a randomised, open-label, phase 2 trial. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Pérez-García%2C+José+Manuel%22">Pérez-García, José Manuel</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cortés%2C+Javier%22">Cortés, Javier</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ruiz-Borrego%2C+Manuel%22">Ruiz-Borrego, Manuel</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Colleoni%2C+Marco%22">Colleoni, Marco</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Stradella%2C+Agostina%22">Stradella, Agostina</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bermejo%2C+Begoña%22">Bermejo, Begoña</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Dalenc%2C+Florence%22">Dalenc, Florence</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Escrivá-de-Romaní%2C+Santiago%22">Escrivá-de-Romaní, Santiago</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Calvo+Martínez%2C+Lourdes%22">Calvo Martínez, Lourdes</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ribelles%2C+Nuria%22">Ribelles, Nuria</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Marmé%2C+Frederik%22">Marmé, Frederik</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cortés%2C+Alfonso%22">Cortés, Alfonso</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Albacar%2C+Cinta%22">Albacar, Cinta</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gebhart%2C+Geraldine%22">Gebhart, Geraldine</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Prat%2C+Aleix%22">Prat, Aleix</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kerrou%2C+Khaldoun%22">Kerrou, Khaldoun</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Schmid%2C+Peter%22">Schmid, Peter</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Braga%2C+Sofia%22">Braga, Sofia</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Di+Cosimo%2C+Serena%22">Di Cosimo, Serena</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gion%2C+Maria%22">Gion, Maria</searchLink> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Lancet%22">Lancet</searchLink>. 4/27/2024, Vol. 403 Issue 10437, p1649-1659. 11p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22F%2E+Hoffmann-La+Roche+Ltd%2E%22">F. Hoffmann-La Roche Ltd.</searchLink><br /><searchLink fieldCode="DE" term="%22Hormone+receptor+positive+breast+cancer%22">Hormone receptor positive breast cancer</searchLink><br /><searchLink fieldCode="DE" term="%22HER2+positive+breast+cancer%22">HER2 positive breast cancer</searchLink><br /><searchLink fieldCode="DE" term="%22Epidermal+growth+factor+receptors%22">Epidermal growth factor receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Progression-free+survival%22">Progression-free survival</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: PHERGain was designed to assess the feasibility, safety, and efficacy of a chemotherapy-free treatment based on a dual human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab and pertuzumab in patients with HER2-positive early breast cancer (EBC). It used an 18fluorine-fluorodeoxyglucose-PET-based, pathological complete response (pCR)-adapted strategy. PHERGain was a randomised, open-label, phase 2 trial that took place in 45 hospitals in seven European countries. It randomly allocated patients in a 1:4 ratio with centrally confirmed, HER2-positive, stage I–IIIA invasive, operable breast cancer with at least one PET-evaluable lesion to either group A, where patients received docetaxel (75 mg/m2, intravenous), carboplatin (area under the curve 6 mg/mL per min, intravenous), trastuzumab (600 mg fixed dose, subcutaneous), and pertuzumab (840 mg loading dose followed by 420 mg maintenance doses, intravenous; TCHP), or group B, where patients received trastuzumab and pertuzumab with or without endocrine therapy, every 3 weeks. Random allocation was stratified by hormone receptor status. Centrally reviewed PET was conducted at baseline and after two treatment cycles. Patients in group B were treated according to on-treatment PET results. Patients in group B who were PET-responders continued with trastuzumab and pertuzumab with or without endocrine therapy for six cycles, while PET-non-responders were switched to receive six cycles of TCHP. After surgery, patients in group B who were PET-responders who did not achieve a pCR received six cycles of TCHP, and all patients completed up to 18 cycles of trastuzumab and pertuzumab. The primary endpoints were pCR in patients who were group B PET-responders after two treatment cycles (the results for which have been reported previously) and 3-year invasive disease-free survival (iDFS) in patients in group B. The study is registered with ClinicalTrials.gov (NCT03161353) and is ongoing. Between June 26, 2017, and April 24, 2019, a total of 356 patients were randomly allocated (71 patients in group A and 285 patients in group B), and 63 (89%) and 267 (94%) patients proceeded to surgery in groups A and B, respectively. At this second analysis (data cutoff: Nov 4, 2022), the median duration of follow-up was 43·3 months (range 0·0–63·0). In group B, the 3-year iDFS rate was 94·8% (95% CI 91·4–97·1; p=0·001), meeting the primary endpoint. No new safety signals were identified. Treatment-related adverse events and serious adverse events (SAEs) were numerically higher in patients allocated to group A than to group B (grade ≥3 62% vs 33%; SAEs 28% vs 14%). Group B PET-responders with pCR presented the lowest incidence of treatment-related grade 3 or higher adverse events (1%) without any SAEs. Among HER2-positive EBC patients, a PET-based, pCR-adapted strategy was associated with an excellent 3-year iDFS. This strategy identified about a third of patients who had HER2-positive EBC who could safely omit chemotherapy. F Hoffmann-La Roche. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/S0140-6736(24)00054-0 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 11 StartPage: 1649 Subjects: – SubjectFull: F. Hoffmann-La Roche Ltd. Type: general – SubjectFull: Hormone receptor positive breast cancer Type: general – SubjectFull: HER2 positive breast cancer Type: general – SubjectFull: Epidermal growth factor receptors Type: general – SubjectFull: Progression-free survival Type: general Titles: – TitleFull: 3-year invasive disease-free survival with chemotherapy de-escalation using an 18F-FDG-PET-based, pathological complete response-adapted strategy in HER2-positive early breast cancer (PHERGain): a randomised, open-label, phase 2 trial. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Pérez-García, José Manuel – PersonEntity: Name: NameFull: Cortés, Javier – PersonEntity: Name: NameFull: Ruiz-Borrego, Manuel – PersonEntity: Name: NameFull: Colleoni, Marco – PersonEntity: Name: NameFull: Stradella, Agostina – PersonEntity: Name: NameFull: Bermejo, Begoña – PersonEntity: Name: NameFull: Dalenc, Florence – PersonEntity: Name: NameFull: Escrivá-de-Romaní, Santiago – PersonEntity: Name: NameFull: Calvo Martínez, Lourdes – PersonEntity: Name: NameFull: Ribelles, Nuria – PersonEntity: Name: NameFull: Marmé, Frederik – PersonEntity: Name: NameFull: Cortés, Alfonso – PersonEntity: Name: NameFull: Albacar, Cinta – PersonEntity: Name: NameFull: Gebhart, Geraldine – PersonEntity: Name: NameFull: Prat, Aleix – PersonEntity: Name: NameFull: Kerrou, Khaldoun – PersonEntity: Name: NameFull: Schmid, Peter – PersonEntity: Name: NameFull: Braga, Sofia – PersonEntity: Name: NameFull: Di Cosimo, Serena – PersonEntity: Name: NameFull: Gion, Maria IsPartOfRelationships: – BibEntity: Dates: – D: 27 M: 04 Text: 4/27/2024 Type: published Y: 2024 Identifiers: – Type: issn-print Value: 01406736 Numbering: – Type: volume Value: 403 – Type: issue Value: 10437 Titles: – TitleFull: Lancet Type: main |
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