Impact of nab-paclitaxel dose reduction on survival of the randomized phase III GeparSepto trial comparing neoadjuvant chemotherapy of weekly nab-paclitaxel (nP) with solvent-based paclitaxel (P) followed by anthracycline/cyclophosphamide for patients with early breast cancer (BC)

Background: The GeparSepto trial demonstrated a higher pathological complete response (pCR) rate after weekly nP compared to P followed by epirubicin (E) plus cyclophosphamide (C) as neoadjuvant treatment for early BC. We report an updated analysis of the key secondary endpoints. Methods: Patients (pts) with histologically confirmed primary BC were randomized 1:1 to either weekly nP 150mg/m2 (nP150) for 12 weeks, after study amendment 125mg/m2 (nP125) or weekly P 80mg/m2 for 12 weeks followed by E 90mg/m2 plus C 600mg/m2 q3w for 4 cycles. Pts with HER2+ BC received concurrent trastuzumab (HerceprinVR ) 6mg/kg (loading (LD) dose 8mg/kg) and pertuzumab 420mg (LD 840mg) q3w. Primary objective was pCR (ypT0 ypN0). Key secondary objectives were disease-free survival (DFS), overall survival (OS), peripheral sensory neuropathy (PSN). DFS rates before and after nP dose reduction are reported. Results: Between 7/2012 and 12/2013, a total of 1229 pts were randomized, 1206 started treatment (nP n=606, P n=600), 455 pts started therapy before and 751 after the amendment. After a median follow-up of 49.7 months (range 0.5-64.0) 248 DFS-events (nP n=103, P n=145) and 137 deaths (nP n=63, P n=74) were reported. Overall, pts with nP had a significantly longer DFS compared to P (HR 0.67 [95%CI 0.52-0.87], p=0.002); OS did not differ between the two arms. The 3-year DFS rates were nP150 85.5% vs P 75.2% (HR 0.66 [95%CI 0.46-0.96], p=0.026) for pts treated before and nP125 88.2% vs P 84.1% (HR 0.68 [95%CI 0.48-0.97], p=0.032) for those after the amendment. Pts treated with nP150 compared to pts with nP125 had less predominant HER2+ BC and Ki67>20% (24.2% vs 38.1%; 60.4% vs 74.3%, respectively), while ER/ PR-negativity was more frequent (36.3 vs 29.0%) (Furlanetto et al. Breast Cancer Res Treat. 2017). PSN resolutions in the two cohorts will be presented at the meeting. Conclusions: The nP dose reduction did not compromise the DFS compared to P. The lower DFS rates with nP150 compared to nP125 can be explained by the different risk profile of the two cohorts.