1. Poster presented at 2013 ASCO Annual Meeting in Chicago, Illinois, May 31 – June 4, 2013 Statistical Methods A prespecified analyses to assess the potential influence of the following prognostic factors on OS and PFS was performed -Age (< 65 and ≥ 65 years) -Sex (male and female) -KPS (70 - 80 and 90 - 100) -Pancreatic cancer primary location (head and other) -Peritoneal carcinomatosis (yes and no) -Presence of liver metastases (yes and no) -Presence of pulmonary metastases (yes and no) -Presence of biliary stent at baseline (yes and no) -Previous Whipple procedure (yes and no) -Number of metastatic sites (1, 2, 3, and > 3) -Stage at diagnosis (IV and other) -CA19-9 level (within normal limit, upper limit of normal (ULN) to < 59 ULN, and ≥ 59 ULN) -Geographic region A Cox proportional hazard model was used to identify potential prognostic factors using a step-wise multivariate analysis with a significance level for entry of 0.2 and for stay of 0.1 INTRODUCTION REFERENCES DISCLOSURES MJM: consultant or advisory role and research funding, Celgene Corp.; DDVH: consultant or advisory role, honoraria, and research funding, Celgene Corp.; TJE: Research funding, Celgene Corp.; FPA: research funding, Clinical Research Alliance and Celgene Corp.; EGC: research funding, Celgene Corp.; JRI: nothing to disclose; JKH: nothing to disclose; MYB: research funding, Celgene Corp.; SRH: nothing to disclose; VG: nothing to disclose; CDW: consultant or advisory role and honoraria, Celgene Corp.; WS: consultant or advisory role, honoraria, and research funding, Celgene Corp.; RKR: consultant or advisory role, honoraria, and research funding, Celgene Corp.; JT: Consultant or advisory role and honoraria, Celgene Corp.; DG: Consultant or advisory role and research funding, Celgene Corp.; XW: employment or leadership position and stock ownership, Celgene Corp.; AR: employment or leadership position and stock ownership, Celgene Corp. Compared with solvent-based paclitaxel, albumin-bound paclitaxel (nab ® - paclitaxel [nab-P], Celgene, Summit, NJ), Exhibits 10-fold higher mean C max of free paclitaxel 1 Delivers 33% higher drug concentration to tumors in preclinical xenograft models 2 Demonstrates enhanced transport across endothelial cell monolayers 2 In this phase III trial (MPACT) of patients with metastatic PC, nab-P + G demonstrated superior efficacy vs G alone Median overall survival (OS): 8.5 vs 6.7 months; HR 0.72; P = 0.000015 Median progression-free survival (PFS): 5.5 vs 3.7 months; HR 0.69; P = 0.000024 Overall response rate (ORR): 23% vs 7%; P = 1.1 × 10 −10 In this analysis, the potential influence of prognostic factors on the primary efficacy endpoint of OS was assessed CONCLUSIONS 1. Gardner ER, et al. Clin Cancer Res. 2008;14:4200-4205. 2. Desai N, et al. Clin Cancer Res. 2006;12:1317-1324. 3. Therasse P, et al. J Natl Cancer Inst. 2000;92:205-216. RESULTS Figure 1. Planned Trial Design Prognostic Factors of Survival in a Randomized Phase III Trial (MPACT) of Weekly nab-Paclitaxel Plus Gemcitabine vs Gemcitabine Alone in Patients With Metastatic Pancreatic Cancer Malcolm J. Moore, 1 Daniel D. Von Hoff, 2 Thomas J. Ervin, 3 Francis P. Arena, 4 E. Gabriela Chiorean, 5 Jeffrey R. Infante, 6 Jeremy K. Hon, 7 Mikhail Yu Biakhov, 8 Sunil R. Hingorani, 9 Vinod Ganju, 10 Colin D. Weekes, 11 Werner Scheithauer, 12 Ramesh K. Ramanathan, 2 Josep Tabernero, 13 David Goldstein, 14 Xinyu Wei, 15 Alfred Romano 15 1 Princess Margaret Hospital, Toronto, ON, Canada; 2 Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare/TGen, Scottsdale, AZ; 3 Florida Cancer Specialists, Englewood, FL; 4 Arena Oncology Associates, Lake Success, NY; 5 University of Washington, Seattle, WA; 6 Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, TN; 7 Clearview Cancer Institute, Huntsville, AL; 8 Semashko Central Clinical Hospital, Moscow, Russia; 9 Fred Hutchinson Cancer Research Center, Seattle, WA; 10 Peninsula Oncology Centre, Frankston, VIC, Australia; 11 University of Colorado Cancer Center, Aurora, CO; 12 Medizinische Universität Wien, Wien, Austria; 13 Vall d'Hebron University Hospital, Barcelona, Spain; 14 Prince of Wales Hospital, Sydney, Australia; 15 Celgene Corporation, Summit, NJ Abstract #4059 nab ® is a registered trademark of Celgene Corporation. KPS, Karnofsky performance status; qw 3/4, first 3 of 4 weeks; qw 7/8, first 7 of 8 weeks; RECIST, Response Evaluation Criteria in Solid Tumors; ULN, upper limit of normal. Table 1. Baseline Characteristics Figure 2. OS in the ITT Population In the phase III MPACT trial KPS, presence of liver metastases, age, region, and number of metastatic sites were found to be the most important predictors of survival Baseline CA19-9 was not an independent predictor of OS in the multivariate analysis; however, the effect of treatment on OS remained significant after baseline CA19-9 was added into the model (HR 0.67; P < 0.0001) After correcting for known prognostic factors, treatment with nab-P + Gem remained an independent, highly significant predictor of improved survival (HR 0.72: P < 0.0001) and disease progression (HR 0.66; P < 0.0001) in patients with metastatic pancreatic cancer STUDY DESIGN ACKNOWLEDGMENTS The authors acknowledge the financial support for this study from Celgene Corporation and the production support from MediTech Media, Ltd. Planned N = 842 Stage IV No prior treatment for metastatic disease KPS ≥ 70 Measurable disease Total bilirubin ≤ ULN Planned N = 842 Stage IV No prior treatment for metastatic disease KPS ≥ 70 Measurable disease Total bilirubin ≤ ULN nab-P 125 mg/m 2 IV qw 3/4 + Gem 1000 mg/m 2 IV qw 3/4 nab-P 125 mg/m 2 IV qw 3/4 + Gem 1000 mg/m 2 IV qw 3/4 Gem 1000 mg/m 2 IV qw 7/8, then qw 3/4 1:1 randomization stratified by: KPS Region Liver metastasis Endpoints Primary: OS Secondary: PFS and ORR by independent review using RECIST v1.0 3 criteria, safety A total of 861 patients were randomized between May, 2009 and April, 2012 in 151 community and academic centers from 11 countries With 608 events, 90% power to detect OS HR = 0.769 (2-sided α = 0.049) Treat until disease progression Events / n (%) Median, mo (95% CI) 75 th Percentile 333 / 431 (77) 8.5 (7.89 - 9.53) 14.8 359 / 430 (83) 6.7 (6.01 - 7.23) 11.4 Months nab-P + Gem Gem HR = 0.72 95% CI (0.617 - 0.835) P = 0.000015 Proportion of Survival 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 036912151821242730333639 1.0 Patient Characteristics nab-P + Gem n = 431 Gem n = 430 All Patients N = 861 Age, median years (min, max) ≥ 65 years old, % 62.0 (27, 86) 41 63.0 (32, 88) 44 63.0 (27, 88) 42 Male, %576058 Region, % North America Australia Eastern Europe Western Europe 62 14 15 9 63 14 9 63 14 15 9 KPS, % 90 – 100 70 - 80 58 42 62 38 60 40 Stage IV at primary diagnosis, %788280 Primary pancreatic tumor location, % Head Body Tail 44 31 24 42 32 26 43 31 25 Current site(s) of metastasis, % Lung Liver Peritoneal carcinomatosis 35 85 4 43 84 2 39 84 3 No. of metastatic sites, % 1 2 ≥ 3 8 47 45 5 48 47 6 47 46 Previous Whipple procedure, %777 Biliary stent, %191617 CA19-9, % Normal > ULN but < 59 × ULN ≥ 59 × ULN 14 28 46 13 28 45 13 28 46 Patients at Risk nab-P + Gem: Gem: 431 430 357 340 269 220 169 124 108 69 67 40 26 27 15 16 7 9 3 4 1 1 0 1 0 0 0 Median OS for nab-P + Gem was significantly longer vs Gem (Figure 2) Figure 3. OS - Prespecified Subgroups nab-P + Gem Events / N Gem Events / N HR 333 / 431359 / 4300.72 188 / 254209 / 2420.65 145 / 177150 / 1880.81 138 / 186141 / 1730.72 195 / 245218 / 2570.72 142 / 179146 / 1610.61 187 / 248212 / 2680.75 142 / 191155 / 1800.59 188 / 237201 / 2460.80 290 / 365309 / 3600.69 43 / 6650 / 700.86 21 / 3316 / 210.41 159 / 202163 / 2060.75 104 / 136121 / 1400.79 49 / 6059 / 630.50 47 / 6043 / 561.07 96 / 12295 / 1200.83 151 / 197171 / 1950.61 50 / 6153 / 590.67 62 / 6459 / 620.84 14 / 3817 / 380.72 207 / 268230 / 2710.68 Group 0.1250.250.51.02.0 HR All Patients Age < 65 Years Age ≥ 65 Years Female Male KPS 70-80 KPS 90-100 Australia Western Europe North America Eastern Europe Primary Tumor Location: Head Primary Tumor Location: Other No Liver Metastases Liver Metastases Normal CA19-9 CA19-9 ULN to < 59 × ULN CA19-9 ≥ 59 × ULN > 3 Metastatic Sites 1 Metastatic Site 3 Metastatic Sites 2 Metastatic Sites Favors Gem Favors nab-P + Gem Factors predictive of OSHazard ratio95% CIP Value Treatment (nab-P + Gem vs Gem)0.720.605 - 0.8490.0001 KPS (70 - 80 vs 90 - 100)1.601.346 - 1.895< 0.0001 Liver metastases (yes vs no)1.811.404 - 2.332< 0.0001 Age (< 65 vs ≥ 65 years)0.810.686 - 0.9670.0190 Region (Eastern Europe vs North America) 1.220.979 - 1.5160.0765 Number of metastatic sites (1, 2, 3, > 3)1.080.988 - 1.1910.0864 Factors predictive of PFSHazard ratio95% CIP Value Treatment (nab-P + Gem vs Gem)0.660.544, 0.796< 0.0001 KPS (70 - 80 vs 90 - 100)1.561.288 - 1.879< 0.0001 Liver metastases (yes vs no)1.791.323 - 2.4240.0002 Age (< 65 vs ≥ 65 years)0.830.683 - 1.0020.0519 Region (Australia vs North America)1.250.963 - 1.6310.0928 Patient Subgroups nab-P + GemGem n Median OS, months n Hazard ratio P Value Region North America Eastern Europe 268 64 8.7 7.7 271 62 6.8 5.9 0.68 0.84 < 0.0001 0.3715 Age < 65 years ≥ 65 years 254 177 9.2 7.8 242 188 6.8 6.6 0.65 0.81 < 0.0001 0.0816 KPS 70 80 90 100 30 149 179 69 3.9 8.1 8.9 12.6 33 128 199 69 2.8 5.6 7.1 10.9 0.99 0.55 0.72 0.92 0.9632 < 0.0001 0.0058 0.6966 Liver metastases Yes No 365 66 8.3 11.0 360 70 5.9 10.7 0.69 0.86 < 0.0001 0.4940 Number of metastatic sites 1 2 3 > 3 33 202 136 60 13.5 8.3 8.0 8.6 21 206 140 63 9.0 7.1 5.9 5.0 0.41 0.75 0.79 0.50 0.0212 0.0150 0.0929 0.0011 Table 2. Stepwise Multivariate Analysis for Predictors of OS and PFS A step-wise multivariate analysis for predictors of OS and PFS are shown in Table 2. -After adding known prognostic factors into the model, the effect of treatment on OS (HR 0.72; 95% CI 0.605 - 0.849, P < 0.0001) and PFS (HR 0.66; 95% CI 0.544, 0.796, P < 0.0001) remained significant and favored nab-paclitaxel treatment across the majority of subgroups. Median OS across subgroups is show in Table 3 Table 3. OS in Subgroups Treatment effect on OS was consistent across patient subgroups (Figure 3) Baseline CA19-9 was found to be a predictor of OS by univariate analysis; however, after correcting for the above factors CA19-9 was not an independent predictor of OS in the multivariate analysis The effect of treatment on OS remained significant after baseline CA19-9 was added into the model (HR 0.67; 95% CI 0.573 - 0.794, P < 0.0001) Copies of this poster obtained through Quick Response (QR) Code are for personal use only and may not be reproduced without permission from ASCO® and the author of this poster