Intense dose-dense epirubicin, paclitaxel, cyclophosphamide versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for neoadjuvant treatment of high-risk early breast cancer (GeparOcto—GBG 84): A randomised phase III trial

Abstract

Background: GeparOcto compared efficacy and safety of two chemotherapy regimens in high-risk early breast cancer (BC): sequential treatment with intense dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) and weekly treatment with paclitaxel plus non-pegylated liposomal doxorubicin (M, Myocetâ) with additional carboplatin (PM(Cb)) in triple-negative BC (TNBC). Patients and methods: Patients with cT1c-cT4a-d and centrally assessed human epidermal growth factor receptor (HER)2-positive BC or TNBC were eligible, irrespective of nodal status, luminal B-like tumours only if pNþ.Patients were randomised (stratified by BC subtype, Ki67, lymphocyte-predominant BC) to receive 18 weeks of E (150 mg/m 2 ) followed by P (225 mg/m 2 ) followed by C (2000 mg/m 2 ), each q2w for 3 cycles or weekly P (80 mg/m 2 ) plus M (20 mg/m 2 ) plus, in TNBC, Cb (area under curve (AUC) 1.5). HER2-positive BC patients additionally received trastuzumab (6 [loading dose 8]mg/kg q3w) and pertuzumab (420 [840]mg q3w) with all P and C cycles. Primary end-point was pathological complete response (pCR, ypT0/is ypN0), secondary endpoints included other pCR definitions, pCR in stratified subpopulations, tolerability and compliance. This trial is registered with ClinicalTrials.gov number NCT02125344. Results: 945/961 randomised patients started treatment. The median age was 48 years; 7.6% had cT3-4, 46% cNþ, 66% G3, 40% HER2-positive, 43% TNBC. pCR rate with iddEPC was 48.3%, with PM(Cb) 48.0%, respectively (PM(Cb) versus iddEPC odds ratio 0.99; 95% confidence interval 0.77e1.28, P Z 0.979) with no significant differences observed in TNBC, HER2-positive, luminal B-like subtypes. 16.4% with iddEPC and 34.1% with PM(Cb) discontinued treatment (P < 0.001), mainly due to adverse events; two patients on PM(Cb) died. Conclusions: In high-risk early BC there is no difference in pCR rates following neoadjuvant treatment with iddEPC or weekly PM(Cb), respectively. iddEPC is one of the effective dosedense regimens feasible in daily practice.

Review A meta-analysis of the efficacy and safety of additional anti-HER2-targeting drugs in HER2-positive advanced breast cancers

“…Speci c AEs such as decreased appetite, vomiting, rash, and diarrhea, which were consistent with the studies of Krop [57] et al In grade 3 and higher AEs, there was no signi cant increase in the overall incidence of AEs, and diarrhea was the only signi cant increase in the speci c AEs. This conclusion was consistent with the study results of Schneeweiss [58] et al We speculated that diarrhea might be related to gastric epidermal cells expressing HER2 [59]. Studies have shown that for elderly patients who are more prone to dehydration, continuous grade 1-2 diarrhea may be debilitating [60], which prompts us to pay more attention to the association between AEs.…”

Efficacy of deescalated chemotherapy according to PAM50 subtypes, immune and proliferation genes in triple‐negative early breast cancer: Primary translational analysis of the WSG‐ADAPT‐TN trial

“…These results are strongly in line with recently published excellent outcome after 18 weeks of docetaxel/carbo backbone without anthracycline use. 20 Although improved pCR under NACT suggests platinumcontaining CHT 12,23,30 as a promising treatment strategy in early TNBC, survival benefits are not yet established 17,18 ; moreover, optimal therapy combinations, 13,14,16 particularly deescalated approaches and predictive markers have yet to be determined. The present translational analysis of the WSG-ADAPT-TN trial has sought to address this need to select patients for deescalated regimens.…”

“…13,14 Replacement of standard weekly solvent-based paclitaxel by nab-paclitaxel (nab-pac), 15 increased dosage of alkylating agents 16 or addition of carboplatin (carbo) to A/T containing NACT 10,17 have led to increased pCR rates (49-60%), albeit with higher toxicity. Such approaches may improve survival in TNBC, [16][17][18] but evidence is not yet conclusive. Remarkably, although BRCA1 mutation-frequently associated with TNBC-is highly predictive for efficacy of carbo as a monotherapy agent, 19 no predictive effect on survival regarding carbo addition has been demonstrated so far in the context of polychemotherapy.…”

Diagnostik und Therapie des triple-negativen Mammakarzinoms (TNBC) – Empfehlungen für die tägliche Routine

“…Ob die Hinzunahme von Platin auch im Rahmen eines dosisdichten/ dosisintensivierten Regimes prognostische Vorteile für die TNBC-Patientinnen bringt, ist derzeit unklar. In der neoadjuvanten GeparOcto-Studie [70] wurden TNBC-Patientinnen entweder mit einer dosisdichten Platin-haltigen Therapie in Kombination mit Anthrazyklinen und Taxanen oder mit dem dosisdichten/ dosisintensivierten ETC-Regime behandelt. Für die TNBC-Patientinnen zeigte sich keine höhere pCR für das Platin-haltige Regime bei insgesamt günstigerem Nebenwirkungsspektrum unter platinfreier Behandlung.…”