1. BACKGROUND & STUDY AIMS TARGETED CHEMOTHERAPY WITH ALBUMIN-BOUND PACLITAXEL (NAB-PACLITAXEL) FOR METASTATIC BREAST CANCER (MBC): WHICH BENEFIT FOR WHICH PATIENTS? A REAL WORLD MULTICENTER ITALIAN EXPERIENCE ON 150 WOMEN R. PALUMBO 1, M.E. CAZZANIGA 2, E. PIAZZA 3, A. FERZI 4, D. GRASSO 5, C. TONDINI 6, M. DANOVA 7, E. TARENZI 8, F. SOTTOTETTI 1, F. VILLA 2, A. GAMBARO 3, F. TOSI 3, C. FASOLA 3, E. ROTA CAREMOLI 4, P. POLETTI 4, C. CAVALLI 7, M. TORCHIO 7 & A. BERNARDO 1 1 Deparmental Unit of Oncology-IRCCS Maugeri Foundation, Pavia; 2 Medical Oncology-San Gerardo Hospital, Monza; 3 Medical Oncology-Luigi Sacco Hospital, Milano; 4 Medical Oncology-Papa Giovanni XXIII Hospital, Bergamo; 5 Medical Oncology-Legnano Hospital; 6 Medical Oncology-IRCCS San Matteo Hospital, Pavia; 7 Medicine and Oncology Unit-Vigevano Hospital, Pavia; 8 Medical Oncology-Falck, Ca’ Granda Hospital, Milano PO62 To provide a picture of “real life clinical practice” we analyzed the different patterns of treatment and outcome of women receiving single-agent Nab-P for their MBC in 8 Centers of Northern Italy from February 2011 to March 2013, with cut-off data evaluation as of February 2014 A subgroup analysis was performed to identify potential prognostic and/or predictive factors for disease outcome and treatment response; PFS and OS were calculated according to the Kaplan-Meyer method Patients received Nab-P as monotherapy intravenously over 30 minutes at the dose of 260 mg/m2 every 3 weeks (85 patients) or 125 mg/m2 weekly (65 patients) at the discretion of the treating oncologist Steroid premedication was not required before therapy infusion Treatment was given in the outpatient setting up to disease progression or unacceptable toxicity or patient refusal 3qw Nab-P 260 mg/m 2 qw Nab-P 125 mg/m 2 OVERALL No of patients (%)8565150 Median age, years [range] <65 years ≥65 years 52 [33-68] 62 (72.9) 23 (27.0) 54 [45-78] 31 (47.7) 34 (52.3) 54 [33-78] 93 (62.0) 57 (38.0) ECOG Performance Status 0 1 2 q3w Nab-P 260 mg/m 2 22 (33.8) 25 (38.4) 18 (27.6) 67 (44.6) 55 (36.6) 28 (18.6) Primary tumour subtype Luminal A Luminal B Triple negative HER2-positive 26 (30.5) 36 (42.3) 21 (24.7) 2 (2.30) 25 (38.4) 20 (30.7) 7 (10.7) 3 (4.60) 51 (34.0) 56 (33.3) 28 (18.6) 5 (3.3) Prior systemic therapy (early stage) anthracycline-based CT (no taxane) anthracycline + taxane taxane only CMF 38 (44.7) 28 (32.9) 11 (12.9) 8 (9.40) 31 (47.6) 24 (36.9) 5 (7.60) 69 (46.0) 52 (34.6) 16 (10.6) 13 (8.6) Median DFI, months (range) ≤24 months >24 months 42 (19-96) 31 (36.4) 54 (63.5) 49 (42-134) 23 (35.3) 42 (64.6) 46 (19-134) 54 (36.0) 96 (64.0) Prior CT for metastatic disease taxane-based without taxane 68 (80.0) 17 (20.0) 34 (52.3) 31 (47.6) 102 (68.0) 48 (32.0) Median n°of prior CT lines for metastatic disease (range) 1 prior CT line 2 prior CT lines 3 prior CT lines ≥4 CT lines 3 (1-5) 46 (54.1) 21 (24.7) 12 (14.1) 6 (7.05) 4 (2-8) 20 (30.7) 10 (15.3) 16 (24.6) 19 (29.2) 3 (1-8) 66 (44.0) 31 (20.6) 28 (18.6) 25 (16.6) Visceral involvement66 (77.6)42 (64.4)108 (72.0) Dominant metastatic sites liver lung bone/nodes skin/soft tissues 38 (44.7) 28 (32.9) 11 (12.9) 8 (9.40) 16 (24.6) 14 (21.5) 25 (38.4) 10 (15.3) 54 (36.0) 42 (28.0) 36 (24.0) 18 (12.0) Number of metastatic sites 1 2 ≥3 14 (16.4) 8 (13.3) 63 (74.1) 17 (26.1) 21 (32.3) 27 (41.5) 31 (20.6) 29 (19.3) 90 (60.0) STUDY POPULATION q3w Nab-P n = 85 qw Nab-P n = 65 OVERALL n = 150 Objective RR (%)47 (55.2)25 (38.4)72 (48.0) Complete response Partial response Stable disease ≥16 weeks Progression disease 5 (5.8) 42 (49.4) 26 (30.5) 12 (14.1) 2 (3.0) 23 (35.3) 25 (38.4) 15 (23.0) 7 (3.2) 65 (44.8) 51(38.4) 27 (18.0) Clinical Benefit rate (CR+PR+SD ≥16 weeks) 73 (85.8)50 (76.9)123 (82.0) Median follow-up Median PFS in the whole population Median PFS in 2 nd line subgroup Median PFS in ≥3 rd line subgroup Median OS 18 months (range 6-30) 7.8 months (3-23+) 12.9 months (6-18+) 4.8 months (4.9) not yet reached q3w Nab-P n = 85 qw Nab-P n = 65 OVERALL n = 150 WHO grade343434 n (%) Anemia1 (1.1)---1 (0.60)- Leukopenia14 (16.4)3 (3.5)2 (3.0)-16 (10.6)3 (2.00) Neutropenia 28 (32.9)18 (21.1)12 (18.4)5 (7.6)40 (32.0)23 (15.3) Thrombocytopenia------ Diarrhea2 (2.30)---2 (2.60)- Nausea/vomiting3 (3.50)-2 (3.00)-5 (3.30)- Mucositis2 (2.30)- 1 (1.50)-3 (2.00)- Fatigue 3 (3.50)-1 (1.50)-4 (2.60)- Sensory neuropathy* 15 (17.6)-8 (12.3)-23 (15.3)- Hypersensitivity reactions ------ Alopecia ** 68 (80.0)- 3 (4.60)-71 (47.3)- Median n° of cycles (range)8 (4-27)5 (3-18)6 (3-27) Required ose reduction (%)17 (20)11 (16.9)28 (18.6) Median treatment duration [months (range)] 8 (6-18)6 (4-15)6 (4-18) * median time to grade ≤ 2: 19 days (range 13-28) ** grade 1-2 in all patients in the q3w cohort AIMS & METHODS STUDY POPULATION AIMS & METHODS TREATMENT ACTIVITYTREATMENT TOXICITY & COMPLIANCE SUBGROUP ANALYSIS Our “real world” experience, consistent with efficacy published results, confirm that Nab-P is a valid chemotherapy option as second and further chemotherapy line in MBC, also for ‘difficult to treat’ populations as taxane-pretreated and triple- negative disease Both the 3-weekly and weekly schedules produced encouraging ORR, PFS and CB values, with globally manageable toxicities and good patient compliance in the outpatient setting, in women given long-term treatment too Although the well known limitations of a retrospective analysis, our cohort represents routine clinical practice, in that it includes women who received multiple lines of treatment (median 3, range 1-7) and who were not participants in controlled clinical trials, thus enhancing the generalizability of findings For clinicians, in the daily decision making, the chance of a flexible schedule of administration allows a better targeted t KEY POINTS FOR CLINICAL PRACTICE age <65 years DFI ≤24 months triple negative subtype predominant visceral disease q3w NAB-Paclitaxel age ≥65 years DFI >4 months ≤ 3metastatic sites no visceral involvement qw NAB-Paclitaxel WHICH SCHEDULE FOR WHICH PATIENTS ? 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