Portal de investigación
A chemotherapy-free, pathological response-adapted strategy using trastuzumab–pertuzumab and T-DM1 in HER2-positive early breast cancer: the PHERGain-2 study?
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Garrigós L.
- Guerrero-Zotano A.
- Cortés-Salgado A.
- Kuemmel S.
- Reboredo-Rendo C.
- Blancas I.
- Carañana V.
- Martínez-de Dueñas E.
- Albacar C.
- Ballesteros-Cidras O.
- Martrat G.
- Boix O.
- Berenguer-Molins P.
- Alcalá-López D.
- Ruiz-Borrego M.
- Pérez-García J.M.
- Guerrero-Zotano Á.
- Kümmel S.
- Colleoni M.
- Bermejo B.
- Gavila J.
- Fabi A.
- Morales C.
- Stradella A.
- Escrivá-de-Romaní S.
- Musolino A.
- Galve-Calvo E.
- Quiroga V.
- Gluz O.
- López González A.
- Ponce-Lorenzo J.
- Cazzaniga M.
- Fischer D.
- Cortez-Castedo P.
- Sanchez-Rovira P.
- Morales S.
- Zamagni C.
- Iranzo V.
- Collovà E.
- Cavanna L.
- Hoffmann O.
- Bassam A.
- García-Sáenz J.
- Medina A.
- Palka M.
- Al-Farhat Y.
- Iacobucci S.
- Cortés J.
- Llombart-Cussac A.
Grupos
Abstract
Background: PHERGain-2 is a multicenter, single-arm, phase II study evaluating a pathologic complete response (pCR)-guided de-escalation strategy to omit chemotherapy in selected patients with HER2-positive early breast cancer (EBC). Patients and methods: Eligible patients were adults, treatment-naive, centrally confirmed HER2-positive (immunohistochemistry 3+), node-negative EBC, with tumors 5-30 mm by magnetic resonance imaging. Patients received eight cycles of neoadjuvant trastuzumab–pertuzumab (HP) (600 mg H + 1200 mg P loading dose, followed by 600 mg H + 600 mg P maintenance dose) every 3 weeks. Patients with hormone receptor (HR)-positive tumors also received endocrine therapy. After surgery, patients received 10 cycles of adjuvant therapy guided by the pathological response: HP for patients with pCR (ypT0/is ypN0) (cohort A), trastuzumab emtansine (T-DM1; 3.6 mg/kg) for patients with residual invasive breast tumors and/or ypN0(i+/mol+), ypN1mi (cohort B), and optional chemotherapy followed by T-DM1 for patients with ypN1-3 (cohort C). Co-primary endpoints were 1-year health-related quality of life (HRQoL) decline (based on the European Organisation for Research and Treatment of Cancer Core Quality of Life questionnaire) and 3-year recurrence-free interval (based on the Standardized Definitions for Efficacy End Points). Key secondary endpoints included overall and HR-specific pCR rates and safety. Results: From August 2021 to March 2024, 396 patients initiated neoadjuvant treatment, 391 (98.7%) underwent surgery. A total of 236 patients (59.6%) achieved pCR (cohort A). Among those with residual disease, 148 (37.8%) entered cohort B and 7 (1.8%) cohort C. One year after initiation of neoadjuvant treatment, =10% decline rate in global HRQoL was 42.8% [95% confidence interval (CI) 36.9% to 48.8%]; 37.3% (95% CI 30.1% to 44.9%) in patients with pCR and 51.9% (95% CI 41.9% to 61.7%) in those with residual disease. Treatment-related adverse events occurred in 86.6% of patients (5.6% grade =3). Serious adverse events occurred in 6.1% of patients. One death (0.3%) due to pneumonitis was attributed to T-DM1. Conclusions: PHERGain-2 shows meaningful HRQoL preservation, expected HP/T-DM1 toxicity, and an outstanding pCR rate comparable with standard chemotherapy plus HP regimens in this patient population. © 2026 The Author(s). Published by Elsevier Ltd on behalf of European Society for Medical Oncology. This is an open access article under the CC BY-NC-ND license. http://creativecommons.org/licenses/by-nc-nd/4.0/
Datos de la publicación
- ISSN/ISSNe:
- 0923-7534, 1569-8041
- Tipo:
- Article
- Páginas:
- 837-848
- PubMed:
- 42097893
- Enlace a otro recurso:
- www.scopus.com
- Factor de Impacto:
- 8,590 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
ANNALS OF ONCOLOGY ELSEVIER
Documentos
- No hay documentos
Filiaciones
Keywords
- de-escalation; early breast cancer; HER2-positive; pathological complete response; trastuzumab emtansine (T-DM1); trastuzumab–pertuzumab