Resumen

Los pacientes con cáncer de mama (CM) primario HER2-positivo que no logran una respuesta completa tras la terapia neoadyuvante adecuada presentan un mayor riesgo de recurrencia de la enfermedad. Se necesitan opciones de tratamiento más eficaces para esta población de pacientes. Este estudio examinará la eficacia y seguridad de trastuzumab deruxtecán (T-DXd) en comparación con trastuzumab emtansina (T-DM1) en pacientes de alto riesgo con cáncer de mama invasivo residual tras la terapia neoadyuvante.

Descripción detallada

Este estudio examinará trastuzumab deruxtecán (T-DXd) frente a trastuzumab emtansina (T-DM1) en pacientes con CM primario HER2-positivo que presentan enfermedad invasiva residual en la mama o los ganglios linfáticos axilares con mayor riesgo de recurrencia, lo que incluye pacientes que eran inoperables en el momento de la presentación de la enfermedad o que presentaban estado ganglionar patológico positivo tras la terapia neoadyuvante. El objetivo primario es comparar la supervivencia libre de enfermedad invasiva (SLEI) entre los brazos de tratamiento con T-DXd y T-DM1 en esta población. El objetivo secundario clave del estudio es evaluar la supervivencia libre de enfermedad (SLE).

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Adults ≥18 years old (local regulatory requirements will apply if the legal age of consent for study participation is \>18 years old).
Pathologically documented HER2-positive breast cancer (BC):
HER2-positive expression defined as an immunohistochemistry (IHC) score of 3+ and/or positive by in situ hybridization (ISH) confirmed prior to study randomization.
Histologically confirmed invasive breast carcinoma.
Clinical stage at disease presentation: T1-4, N0-3, M0; patients presenting with T1N0 tumors are not eligible.
Pathologic evidence of residual invasive carcinoma in the breast and/or axillary lymph nodes following completion of neoadjuvant therapy meeting one of the following high-risk criteria:
Inoperable breast cancer at presentation (prior to neoadjuvant therapy), defined as clinical stages T4, N0-3, M0 or T1-3, N2-3, M0.
Operable at presentation, defined as clinical stages T1-3,N0-1,M0, with axillary node positive disease (ypN1-3) following neoadjuvant therapy.
Completion of neoadjuvant systemic therapy, including taxane-based chemotherapy and HER2-directed treatment prior to surgery.
Systemic therapy must consist of at least 6 cycles of neoadjuvant therapy with a total duration of at least 16 weeks, including at least 9 weeks of trastuzumab (± pertuzumab) and at least 9 weeks of taxane-based chemotherapy to be completed prior to surgery. Patients may have received an anthracycline as part of neoadjuvant therapy in addition to taxane chemotherapy.
Adequate excision as confirmed per medical records: surgical removal of all clinically evident disease in the breast and axillary lymph nodes.
An interval of no more than 12 weeks between the date of last surgery and the date of randomization.
Known hormone receptor (HR) status, per local laboratory assessment, as defined by ASCO-CAP guidelines (≥1%): HR positive status defined by either positive estrogen receptor (ER) and/or positive progesterone receptor (PR).
status. HR-negative status defined by both known negative ER and known negative PR.
Left ventricular ejection fraction (LVEF) ≥50% within 28 days prior to randomization.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at Screening.
Has adequate organ function within 14 days before randomization.

Criterios de exclusión

Stage IV (metastatic) BC.
History of any prior (ipsi- or contralateral) breast cancer except lobular carcinoma in situ (LCIS).
Evidence of clinically evident gross residual or recurrent disease following neoadjuvant therapy and surgery.
Prior treatment with T-DXd, T-DM1 or other anti-HER2 antibody-drug conjugate (ADC) or prior enrollment in a clinical study of T-DXd (regardless of treatment arm)
History of exposure to the following cumulative doses of anthracyclines:
Doxorubicin \> 240 mg/m\^2
Epirubicin or Liposomal Doxorubicin-Hydrochloride \> 480 mg/m\^2
For other anthracyclines, exposure equivalent to doxorubicin \> 240 mg/m\^2
History of other malignancy within the last 5 years except for appropriately treated CIS of the cervix, nonmelanoma skin carcinoma, Stage I melanoma skin carcinoma, Stage I uterine cancer, or other appropriately treated non-breast malignancies with an outcome similar to those mentioned above.
History of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids and/or has ILD/pneumonitis noted on computed tomography (CT) scan of the chest at Screening (asymptomatic interstitial changes confined to recent radiation therapy fields are not excluded).
Known pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within three months prior to randomization, severe asthma, severe chronic obstructive pulmonary disease \[COPD\], restrictive lung disease).
Any autoimmune, connective tissue or inflammatory disorders (eg, Rheumatoid arthritis, Sjogren's, sarcoidosis, etc) where there is documented or a suspicion of pulmonary involvement or pneumonectomy at the time of screening.
Medical history of myocardial infarction (MI) within 6 months before randomization, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV), troponin levels consistent with MI as defined according to the manufacturer 28 days prior to randomization.

Ubicaciones

Centro Oncologico Riojano Integral

Capital, La Rioja Province, Argentina

Sanatorio Británico de Rosario

Rosario, Santa Fe Province, Argentina

Instituto de Oncología de Rosario

Rosario, Santa Fe Province, Argentina

COIBA

Buenos Aires, Argentina

Instituto Alexander Fleming

Caba, Argentina

CER San Juan

San Juan, Argentina