Fernando De Vita Oncologia Medica Seconda Università di Napoli Esperienza real life A multicenter experience of Nab-paclitaxel plus Gemcitabine as first-line therapy in mPC: efficacy and safety results in clinical practice Fernando De Vita Oncologia Medica Seconda Università di Napoli

Esperienza real life – I linea Inclusion criteria 46 pts with mPC who received Nab-paclitaxel and Gemcitabine between January 2012 and December 2014 were selected as the subjects of this study according to the following criteria: histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas ECOG PS ≤ 2 age ≥ 18 adequate major organ functions no previous CT; gemcitabine in the adjuvant setting was allowed if the treatment was completed at least 6 months before written informed consent

Esperienza real life – I linea Treatment schedule Nab-paclitaxel/Gemcitabine Nab-paclitaxel 125 MG/M2 D1,8,15 Gemcitabine 1000 MG/M2 D1,8,15 every 4 weeks

Esperienza real life – I linea Endpoints The purposes of the present study were to evaluate the effectiveness of NAB-P/GEM regimen in an unselected population of patients with metastatic PC and to identify the prognostic factors influencing outcome Endpoints Overall Response Rate (ORR) Progression Free Survival (PFS) Overall Survival (OS) Toxicity Prognostic factors analysis The data on the patient background characteristics, adverse events, treatment compliance, treatment response, progression-free survival (PFS) and overall survival (OS) were collected retrospectively from the medical records

Esperienza real life – I linea Pretreatment evaluation *CT scan of the chest and abdomen/pelvis Blood count, serum chemistry and tumor markers (*CA 19-9) ECG and echocardiogram with evaluation of ventricular function *tumor response evaluated every 8 weeks by CT scan and CA 19-9

Patients characteristics (1) Esperienza real life – I linea Baseline characteristichs Patients characteristics (1) PTS 46 AGE (range) >70 63 (41-77) 11 (23.9%) SEX M F 22 (47%) 24 (63%) PS (ECOG) 1 2 21 (45.6%) 15 (32.6%) 10 (21.7%) PANCREATIC PRIMARY LOCATION HEAD BODY/TAIL 28 (61%) 18 (39%)

Patients characteristics (2) Esperienza real life – I linea Baseline characteristichs Patients characteristics (2) SITE OF METASTASIS Lung Liver Peritoneum Bone 9 (19.5%) 32 (69.5%) 6 (13%) 1 (2%) No OF METASTATIC SITES 1 ≥ 2 31 (67%) 15 (33%) BILIARY STENT 11 (24%) MEDIAN CA19.9 U/I (range) 469 (17.4 - 61546) PREVIOUS SURGERY 11 (24%) PREVIOUS ADJUVANT GEMCITABINE 10 (22%)

Esperienza real life – I linea Cross trial comparison comparison between poor PTS characteristics CHARACTERISTIC MPACT Our experience ECOG 2 (%) 8 21.7 AGE >70 (%) 10 23.9 BILIARY STENT (%) 19 24 PREVIOUS ADJUVANT CT (%) 22 HEAD 44 61 PERITONEUM 4 13

Esperienza real life – I linea Overall Response Rate (ORR) RC 2 (4.3%) RP 14 (30.4%) 16 (34.7%) SD 17 (36.9%) DCR 33 (71.7%) PD 13 (28.2%) *CA19.9 ≥ 50% reduction 20 (43.4%) *correlation between CA19.9 decrease ≥ 50% from baseline and tumor response (Pearson correlation 0.581, Sig. 2 tails 0.0001)

Esperienza real life – I linea Progression Free Survival (PFS) PFS, months (update data January 2015) PFS, months Median Range (95% CI) 6.9 (3-14)

Esperienza real life – I linea PFS: univariate analysis VARIABLE P ECOG (PS 0-1 vs 2) 0.043 AGE (<70 vs > 70) 0.989 SEX (M vs F) 0.126 Tumor Site (Head vs Other) 0.116 Bilirubin (> ULN vs < ULN) 0.05 Byliary Stent (No vs Yes) 0.365 Liver Metastasis (No vs Yes) 0.119 Multiple Metastasis (No vs Yes) 0.794 Basal Ca 19.9 (> 59ULN vs ≤ 59ULN) 0.741 Ca 19.9 Response (<50% vs >50%) 0.006 NLR ( <5 vs >5) 0.011

Esperienza real life – I linea PFS according NLR Median (95% CI) Range <5 8.0 6.9-9.0 >5 3.0 0.8-5.1 Log Rank test: P: 0.005

Esperienza real life – I linea PFS according CA 19.9 response Median (95% CI) Range Response <50% 4.0 0.7-7.2 >50% 9.0 6.5-11.5

MULTIVARIATE ANALYSIS Esperienza real life – I linea PFS: multivariate analysis MULTIVARIATE ANALYSIS VARIABLE P ECOG 0.125 CA 19.9 response 0.006 NLR 0.002 Bilirubin 0.444

Esperienza real life – I linea Overall survival OS, months Median Range (95% CI) 10.5 7.8-13 OS, months (update data January 2015) 3 (7.3 %) 13 (31.7%) 3 (7.3%)

Esperienza real life – I linea OS: univariate analysis VARIABLE P ECOG (PS 0-1 vs 2) 0.02 AGE (<70 vs > 70) 0.56 SEX (M vs F) 0.23 Tumor Site (Head vs Other) 0.22 Bilirubin (> ULN vs < ULN) 0.12 Byliary Stent (No vs Yes) 0.77 Liver Metastasis (No vs Yes) 0.24 Multiple Metastasis (No vs Yes) 0.82 Basal Ca 19.9 (> 59ULN vs ≤ 59ULN) 0.25 Ca 19.9 Response (<50% vs >50%) 0.04 NLR ( <5 vs >5) 0.001

Esperienza real life – I linea OS according NLR Median (95% CI) Range <5 12.0 9.3-14.6 >5 7.0 3.8-10.1 Log Rank test, P: 0.0001

MULTIVARIATE ANALYSIS Esperienza real life – I linea OS: multivariate analysis MULTIVARIATE ANALYSIS VARIABLE P ECOG 0.03 CA 19.9 response 0.15 NLR 0.002

Esperienza real life – I linea Second-line CT

Esperienza real life – I linea Treatment exposure Total number of cycles: 273 Median number of cycles: 6 (range 1 – 14)

Esperienza real life – I linea Toxicity AE nab-P + Gem (n = 46) Grade 3 hematologic AE, no (%) Anemia 7 (15.2%) Neutropenia 12 (26%) Thrombocytopenia 8 (17.3%) Grade 3 non hematologic AE, no (%) Fatigue Peripheral neuropathy 6 (13%) Diarrhea 7 (15%) Nausea 6 (13%)

Esperienza real life – I linea Conclusions Our results indicate that Nab-P + Gem is an effective treatment with the potential for long-term survivors also in the clinical practice including elderly and poor PS pts Availability of Nab-P + Gem as an effective first-line may conceivably allow maintenance of a better PS, thus increasing the chance of exposing pts to subsequent treatment lines, with consequent benefit in terms of OS This study provides safety data similar to those of the pivotal MPACT phase III trial Exploratory analyses suggest that PS and NLR are independent predictor of OS  

Esperienza real life – I linea Oncologia Medica Seconda Università di Napoli Jole Ventriglia Angelica Petrillo Alessio Fabozzi Ospedale Sacro Cuore di Gesù - Benevento Antonio Febbraro Guido Giordano La realta' e' determinata non da quello che gli scienziati o chiunque altro dice o crede ma da quello che le prove ci rivelano. Alan Hale 

Esperienza real life – I linea Background “In the era of biologic and molecularly targeted agents, the success of nab-paclitaxel in recalcitrant pancreatic cancer is a timely reminder of the importance and relevance of pharmacology and novel drug delivery technology in the development of anticancer drugs.”