Background: Based on the results of the single-arm phase II APT trial, the combination of 12 cycles of weekly Paclitaxel-Trastuzumab (APT), followed by the administration of Trastuzumab until the completion of one year of treatment, is recommended for most stage I HER2+ breast cancers. Confirming the efficacy of this regimen in an independent real-world cohort of patients is therefore of great interest. Materials and methods: This monocentric, retrospective, real-world study included patients diagnosed with early-stage HER2+ breast cancer (pT≤3 cm; pN0/N1mic – in line with the inclusion criteria of the APT study) who began adjuvant treatment with the APT regimen at the Istituto Oncologico Veneto IRCCS from 01/2014 to 10/2023. Patients with bilateral breast cancer, concomitant diagnosis of a second HER2- breast cancer, with previous history of breast cancer or previously treated with chemotherapy for other malignancy were excluded. Data were collected from medical records in pseudo-anonymized form. Recurrence-free survival (RFS), distant relapse-free survival (DRFS), and overall survival (OS), defined according to STEEP criteria (Tolaney et al, 2021), were evaluated. Results: The study included 276 patients. The median age was 56 years (range 26-83). Most patients presented hormone receptor (HR) positive breast cancer (75.0%, N=207), histologic grade G3 (65.6%, N=181), tumor size pT≤ 2 cm (92.4%, N=255) and no lymph node involvement (only 6.9% of patients presented with a N1mic nodal stage). At a median follow-up of 3.9 years (IQR 3.5-4.2), the 3-years RFS rate was 97.1% (95% CI=94.7-99.5), the 3-years DRFS rate was 97.5% (95% CI=95.3-99.7), and the 3-years OS rate was 99.0% (95% CI=97.6-100). No significant differences were observed in RFS based on HR status, histological grade, HER2 expression evaluated by immunohistochemistry (IHC 3+ vs IHC 2+/ISH amplified), menopausal status, and age. However, a statistically significant difference in RFS was observed based on anatomical stage (pTNM, log-rank p<0.001), with 3-year RFS rates of 98.8% (95% CI=97.0-100) for stage IA, 84.8% (95% CI=65.2-100) for stage IB, and 88.2% (95% CI=72.9-100) for stage IIA HER2+ breast cancer. This significant difference in oncological outcomes based on anatomical stage was also confirmed for DRFS, while potential impact on OS was not evaluated (due to the extremely limited number of events). Regarding cardiological adverse events, only 1 patient (0.4%) developed symptomatic heart failure, and 3 patients (1.1%) experienced an asymptomatic reduction in left ventricular ejection fraction. Conclusions: At a still limited follow-up, the results of this real-world study confirm the good oncological outcomes achieved by the APT regimen in patients with stage I HER2+ breast cancer. Additionally, it also confirms good cardiological tolerance in a less selected real-world patient population. The poorer outcomes observed in patients with more extensive stage disease (stage IB or stage IIA with pT≤3 cm) suggest that this therapeutic regimen should be used with extreme caution in this context, although these patients were included in the pivotal study.
Background: Sulla base dei risultati dello studio a singolo braccio di fase II APT, la combinazione di 12 cicli settimanali di Paclitaxel-Trastuzumab (APT), seguita dalla somministrazione di Trastuzumab fino a completamento dell’anno, rappresenta il trattamento raccomandato per la maggior parte dei carcinomi mammari HER2-positivi in stadio I. La conferma dell’efficacia di tale regime anche in coorti indipendenti da pratica clinica risulta pertanto di particolare interesse. Materiali e metodi: Questo studio monocentrico, retrospettivo, real-world ha incluso pazienti con diagnosi di carcinoma mammario HER2-positivo in stadio iniziale (pT≤3 cm, pN0/N1mic – in linea con i criteri di inclusione dello studio APT) che hanno iniziato trattamento adiuvante secondo regime APT presso l’Istituto Oncologico Veneto IRCCS dal 01/2014 al 10/2023. Sono stati esclusi pazienti con diagnosi di carcinoma mammario bilaterale, diagnosi concomitante di carcinomi mammari HER2-, con precedente storia di carcinoma mammario o precedentemente trattati con chemioterapia per altre neoplasie. I dati sono stati raccolti dalle cartelle cliniche in forma pseudo-anonimizzata. Gli outcome oncologici valutati sono stati la sopravvivenza libera da recidiva (RFS), la sopravvivenza libera da recidiva a distanza (DRFS) e la sopravvivenza globale (OS), definite secondo i criteri STEEP (Tolaney et al, 2021). Risultati: Lo studio ha incluso 276 pazienti. L’età mediana era di 56 anni (range 26-83). La maggior parte dei pazienti presentava un carcinoma mammario recettori ormonali (HR) positivo (75,0%, N=207), un grado istologico G3 (65,6%, N=181), dimensione tumorale pT≤ 2 cm (92,4%, N=255) ed assenza di coinvolgimento linfonodale (solo il 6,9% dei pazienti presentava uno stadio linfonodale N1mic). Ad un follow-up mediano di 3,9 anni (IQR 3,5-4,2), il tasso di RFS a 3 anni è risultato del 97,1% (95% CI=94,7-99,5), di DRFS a 3 anni del 97,5% (95% CI=95,3-99,7) e la OS a 3 anni è risultata del 99,0% (95% CI=97,6-100). Non sono state osservate significative differenze nella RFS in base allo stato dei recettori ormonali, al grado istologico, all’espressione di HER2 all’immunoistochimica (IHC 3+ vs IHC 2+/ISH amplificato), allo stato menopausale e all’ età. Si è invece osservata una differenza statisticamente significativa nella RFS in base allo stadio anatomico (pTNM, log-rank p< 0,001), con tassi di RFS a 3 anni del 98,8% (95% CI=97,0-100) per pazienti diagnosticati con neoplasie stadio IA, dell’84,8% (95% CI=65,2-100) per pazienti diagnosticati con neoplasie stadio IB e dell’88,2 % (95% CI=72,9-100) per pazienti diagnosticati con neoplasie stadio IIA. Tale differenza significativa negli outcome oncologici sulla base dello stadio anatomico si è anche confermata per quanto riguarda la DRFS, mentre non è stato valutato il possibile impatto sull’OS (per numero di eventi estremamente limitato). Per quanto riguarda gli effetti avversi cardiologici, solo 1 paziente (0,4%) ha presentato un’insufficienza cardiaca sintomatica e 3 pazienti (1,1%) hanno presentato una riduzione asintomatica della frazione di eiezione del ventricolo sinistro. Conclusioni: I risultati di questo studio di real-world, seppur ad un follow-up ancora limitato, confermano i buoni outcome oncologici del regime APT in pazienti con carcinoma mammario HER2+ in stadio I. Inoltre, è confermata la buona tolleranza cardiologica in una popolazione meno selezionata di pazienti real-world. I peggiori outcome osservati invece nei pazienti con neoplasia in stadio più esteso (stadio IB o stadio IIA con pT≤ 3 cm) suggeriscono che tale regime terapeutico dovrebbe essere utilizzato con estrema cautela in questo contesto, sebbene tali pazienti fossero includibili nello studio pivotale.
Trattamento adiuvante con Paclitaxel-Trastuzumab per carcinomi mammari HER2-positivi in stadio iniziale: uno studio retrospettivo real-world
GASPARI, ANNA
2023/2024
Abstract
Background: Based on the results of the single-arm phase II APT trial, the combination of 12 cycles of weekly Paclitaxel-Trastuzumab (APT), followed by the administration of Trastuzumab until the completion of one year of treatment, is recommended for most stage I HER2+ breast cancers. Confirming the efficacy of this regimen in an independent real-world cohort of patients is therefore of great interest. Materials and methods: This monocentric, retrospective, real-world study included patients diagnosed with early-stage HER2+ breast cancer (pT≤3 cm; pN0/N1mic – in line with the inclusion criteria of the APT study) who began adjuvant treatment with the APT regimen at the Istituto Oncologico Veneto IRCCS from 01/2014 to 10/2023. Patients with bilateral breast cancer, concomitant diagnosis of a second HER2- breast cancer, with previous history of breast cancer or previously treated with chemotherapy for other malignancy were excluded. Data were collected from medical records in pseudo-anonymized form. Recurrence-free survival (RFS), distant relapse-free survival (DRFS), and overall survival (OS), defined according to STEEP criteria (Tolaney et al, 2021), were evaluated. Results: The study included 276 patients. The median age was 56 years (range 26-83). Most patients presented hormone receptor (HR) positive breast cancer (75.0%, N=207), histologic grade G3 (65.6%, N=181), tumor size pT≤ 2 cm (92.4%, N=255) and no lymph node involvement (only 6.9% of patients presented with a N1mic nodal stage). At a median follow-up of 3.9 years (IQR 3.5-4.2), the 3-years RFS rate was 97.1% (95% CI=94.7-99.5), the 3-years DRFS rate was 97.5% (95% CI=95.3-99.7), and the 3-years OS rate was 99.0% (95% CI=97.6-100). No significant differences were observed in RFS based on HR status, histological grade, HER2 expression evaluated by immunohistochemistry (IHC 3+ vs IHC 2+/ISH amplified), menopausal status, and age. However, a statistically significant difference in RFS was observed based on anatomical stage (pTNM, log-rank p<0.001), with 3-year RFS rates of 98.8% (95% CI=97.0-100) for stage IA, 84.8% (95% CI=65.2-100) for stage IB, and 88.2% (95% CI=72.9-100) for stage IIA HER2+ breast cancer. This significant difference in oncological outcomes based on anatomical stage was also confirmed for DRFS, while potential impact on OS was not evaluated (due to the extremely limited number of events). Regarding cardiological adverse events, only 1 patient (0.4%) developed symptomatic heart failure, and 3 patients (1.1%) experienced an asymptomatic reduction in left ventricular ejection fraction. Conclusions: At a still limited follow-up, the results of this real-world study confirm the good oncological outcomes achieved by the APT regimen in patients with stage I HER2+ breast cancer. Additionally, it also confirms good cardiological tolerance in a less selected real-world patient population. The poorer outcomes observed in patients with more extensive stage disease (stage IB or stage IIA with pT≤3 cm) suggest that this therapeutic regimen should be used with extreme caution in this context, although these patients were included in the pivotal study.File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.12608/65742