Long-term follow-up of the anthracyclines in early breast cancer trials (USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 [NRG Oncology])

Messaggi chiave

Gli studi Anthracyclines in Early Breast Cancer (ABC) hanno confrontato l’efficacia di 6 cicli di docetaxel e ciclofosfamide (TC6) rispetto al regime standard di docetaxel o paclitaxel con ciclofosfamide e doxorubicina (TaxAC) nel trattamento adiuvante del carcinoma mammario precoce ad alto rischio.
L’analisi aggregata finale dei risultati dei tre studi, condotta a un follow-up mediano di 6,9 anni, conferma i dati pubblicati nel 2017, non riuscendo a dimostrare la non inferiorità di TC6 rispetto a TaxAC in termini di sopravvivenza libera da malattia invasiva (IDFS) (hazard ratio [HR]: 1,14; IC 80%, 1,04-1,25, rispetto a una soglia di inferiorità predefinita di 1,18).
È stata osservata una differenza significativa a favore di TaxAC in termini di intervallo libero da recidiva (HR, 1,38 [IC 95%, 1,16-1,65]; p = 0,0003), senza tuttavia alcuna differenza in sopravvivenza globale. La revisione degli eventi di IDFS osservati suggerisce che il minor numero di recidive tumorali ottenuto con i regimi antraciclinici potrebbe essere controbilanciato da un aumento del rischio di leucemie tardive e decessi non correlati al tumore primario.

The primary joint efficacy analysis of the Anthracyclines in Early Breast Cancer (ABC) trials reported in 2017 failed to demonstrate nonanthracycline adjuvant therapy was noninferior to anthracycline-based regimens in high-risk, early breast cancer.
Full analyses of the studies had proceeded when the prespecified futility boundary was crossed at a planned futility analysis for the ability to demonstrate noninferiority of a nonanthracycline regimen with continued follow-up.
These results were presented with 3.3 years of median follow-up.
This manuscript reports results of the final analyses of the study efficacy end points conducted with 6.9 years of median follow-up.
Long-term analysis of invasive disease-free survival (IDFS), the primary end point of the ABC trials, remains consistent with the original results, as noninferiority of the nonanthracycline regimens could not be declared on the basis of the original criteria.
The secondary end point of recurrence-free interval, which excluded deaths not due to breast cancer as events, favored anthracycline-based regimens, and tests for heterogeneity were significant for hormone receptor status (p = 0.02) favoring anthracycline regimens for the hormone receptor-negative cohorts.
There was no difference in overall survival, and review of the type of IDFS events in the groups suggested reductions in cancer recurrences achieved with anthracycline regimens were offset by late leukemias and deaths unrelated to breast cancer.