Abstract P6-14-01: The effect trial: A randomized phase II trial evaluating two different doses of weekly (W) NAB-paclitaxel (NP) as first-line chemotherapy in older breast cancer (BC) patients (pts)
Authors: Biganzoli L , Berardi R , Pedersini R , Minisini AM , Caremoli ER , Spazzapan S , Lima JS , Baldari D , Orlando L , Magnolfi E , Pistelli M , Brunello A , Zafarana E , Bernardo A , Leo S , Colleoni M , Donati S , De Placido S , Parolin V , Vitale S , Di Leo A , Puglisi F , Boni L , Cinieri S 
Published: February 2018

Abstract
Background: W taxanes (T) are commonly used in the treatment of older BC pts, with neurotoxicity (NTX) and fatigue being dose-limiting toxicities with a possible negative impact on function. No prospective data exists on the safety and efficacy of W NP in this population. NP might be of particular value in older pts, due to no need for premedication with steroids and shorter time to recovery from neurotoxicity than conventional T, resulting in a reduced risk of exacerbation of comorbidities such as hypertension and diabetes, and possibly of functional decline (FD). Methods: Pts aged ≥ 65 years (y) with Her-2 negative or Her-2 positive (+), but contraindicated to anti-Her-2 therapy, advanced BC were randomized to receive NP as first-line chemotherapy at either 100 (Arm A) or 125 mg/m2 (Arm B), days 1, 8, 15 q 28. The primary end-point was event-free survival (EFS). An event was either disease progression (PD), death, or FD - defined as a decrease of at least 1 point from baseline values of activities of daily living (ADL) or instrumental ADL (IADL), deemed by the investigator as treatment-related and confirmed at the subsequent cycle. Secondary endpoints included progression-free survival (PFS), response rate (RR) in pts with measurable disease, and incidence of adverse events (AEs). Results: From January 2013 to September 2016, 160 pts were randomized in 15 Italian centres; all but 2 who never started NP were eligible for final analysis. Pts median age was 72y (range 65-84) in Arm A and 73y (range 65-88) in Arm B. Median ECOG performance status was 0 (range 0-2). Baseline IADL impairment was reported in 20 pts (25%) in both arms. &gt;80% pts had ER+ tumors; 2 pts had HER2+ disease. Visceral disease was present in 71% (Arm A) and 70% (Arm B) of pts. Prior exposure to T in the neo/adjuvant setting was 14% (Arm A) and 13% (Arm B). Median number of delivered cycles of NP was 6 (range 1-28 in Arm A, and 1-22 in Arm B), with 3 pts still on treatment. Dose reductions were similarly reported (72% of pts Arm A, 78% of pts Arm B). At a median follow-up of 21 months (mos) (Interquartile range 14-28.4) 140 events were observed. Arm A/Arm B: PD n=53(67%)/n=52(66%); FD n=13(15%)/n=14(18%), death n=3(4%)n=5(6%). Outcomes data are reported in the following table:
Outcomes Arm AArm BMedian EFS, mos (90% CI)6.2 (5.5-8.4)6.4 (5.8-7.7)Median PFS, mos (95% CI)8.3 (5.9-10.5)8.8 (7.4-10.3)RR (95% CI)37% (25-50)42% (30-54)
Fatigue (Arm A: grade (G)2 29%, G3 11%; Arm B: G2 46%, G3 5%) and NTX (Arm A: G2 15%, G3 4%; Arm B: G2 28%, G3 8%) were the most frequently reported AEs. No G4 AEs were reported with the exception of neutropenia (1 pt in arm A) and leucopenia (3 pts in Arm A, 1 pt in arm B). 1 G5 (sepsis) was recorded in Arm B. NTX was reported as the reason for treatment discontinuation in 21 pts (13%) of whom 16 (21%) in arm B. Conclusion: Looking at classical study endpoints (PFS, RR), both doses of NP are active in older pts. However, 17% of pts had to stop treatment due to FD, assessed according to predefined criteria. Due to similar efficacy and reduced NTX, W NP 100 is the suggested dose to be used in older pts with advanced BC.
Citation Format: Biganzoli L, Berardi R, Pedersini R, Minisini AM, Caremoli ER, Spazzapan S, Lima JS, Baldari D, Orlando L, Magnolfi E, Pistelli M, Brunello A, Zafarana E, Bernardo A, Leo S, Colleoni M, Donati S, De Placido S, Parolin V, Vitale S, Di Leo A, Puglisi F, Boni L, Cinieri S. The effect trial: A randomized phase II trial evaluating two different doses of weekly (W) NAB-paclitaxel (NP) as first-line chemotherapy in older breast cancer (BC) patients (pts) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-14-01.