Survival analysis of the randomised phase III GeparOcto trial comparing neoadjuvant chemotherapy of intense dose-dense epirubicin, paclitaxel, cyclophosphamide versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for patients with high-risk early breast cancer
Mené sur 945 patientes atteintes d'un cancer du sein de stade précoce à haut risque de récidive, cet essai de phase III compare l'efficacité, du point de vue du délai avant la survenue d'événéments indésirables, d'une chimiothérapie néoadjuvante à doses intensifiées d'épirubicine, de paclitaxel et de cyclophosphamide et d'une chimiothérapie néoadjuvante hebdomadaire combinant paclitaxel et doxorubicine liposomale (durée médiane de suivi : 47 mois)
Background : GeparOcto demonstrated that pathological complete response (pCR) of intense dose-dense epirubicin, paclitaxel and cyclophosphamide (iddEPC) was comparable to weekly paclitaxel/non-pegylated liposomal doxorubicin (plus carboplatin (PM(Cb) in triple-negative breast cancer [TNBC])in high-risk early breast cancer (BC). Here, we report time-to-event secondary end-points. Patients and methods : Patients were randomised to receive 18 weeks of E (150 mg/m2) followed by P (225 mg/m2) followed by C (2000 mg/m2), each q2w or weekly P (80 mg/m2) plus M (20 mg/m2) plus, in TNBC, Cb (AUC 1.5). Patients with human epidermal growth factor receptor2-positive (HER2+)BC received trastuzumab (6[loading dose 8]mg/kg q3w) and pertuzumab(420[840]mg q3w) with P and C cycles. Results : 945 patients started treatment (iddEPC n = 470; PM(Cb) n = 475). After a median follow-upof 47.0 (range 1.6–61.5) months, 162 (75 in iddEPC; 87 in PM(Cb)) invasive disease-freesurvival (iDFS) events and 79 (41 in iddEPC; 38 in PM(Cb)) deaths were reported. Nosignificant difference was observed in 4-year iDFS (81.9% iddEPC versus 79.7% PM(Cb),HR = 1.16 [95%CI 0.85–1.59], log-rank p = 0.334) or 4-year overall survival (OS) (90.3%iddEPC versus 90.6% PM(Cb), HR = 0.90 [95%CI 0.58–1.40], log-rank p = 0.637) overalland in HER2+ and TNBC subgroups. HR+/HER2- BC patients, however, had significantlybetter 4-year iDFS (77.9% iddEPC versus 62.5% PM, HR = 2.11 [95%CI 1.08–4.10], log-rankp = 0.025) and 4-year OS with iddEPC (94.7% iddEPC versus 80.1% PM, HR = 3.26 [95%CI1.06–10.00], log-rank p = 0.029). Conclusion : While there was no difference in survival for the entire cohort, the HR+/HER2-subgroupsignificantly benefits from iddEPC. This supports the concept of an additional effectof NACT beyond pCR in patients with HR+/HER2- BC.