Results of a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone for patients with metastatic adenocarcinoma of the pancreas with PET and CA19-9 correlates.

Author:

Von Hoff Daniel D.1,Ervin Thomas J.2,Arena Francis P.3,Chiorean E. Gabriela4,Infante Jeffrey R.5,Moore Malcolm J.6,Seay Thomas E.7,Tjulandin Sergei8,Ma Wen Wee9,Saleh Mansoor N.10,Harris Marion11,Reni Michele12,Ramanathan Ramesh K.13,Tabernero Josep14,Hidalgo Manuel15,Van Cutsem Eric16,Goldstein David17,Wei Xinyu18,Iglesias Jose Luis19,Renschler Markus Frederic18

Affiliation:

1. Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare/TGen, Scottsdale, AZ

2. Florida Cancer Specialists, Englewood, FL

3. Arena Oncology Associates, Lake Success, NY

4. University of Washington, Seattle, WA

5. Sarah Cannon Research Institute; Tennessee Oncology, Nashville, TN

6. Princess Margaret Hospital, Toronto, ON, Canada

7. Atlanta Cancer Care, Atlanta, GA

8. N. N. Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russia

9. Roswell Park Cancer Institute, Buffalo, NY

10. Georgia Cancer Specialists PC, Atlanta, GA

11. Southern Health, East Bentleigh, VIC, Australia

12. Ospedale San Raffaele, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy

13. Virginia G. Piper Cancer Center at Scottsdale Healthcare/TGen, Scottsdale, AZ

14. Vall d'Hebron University Hospital, Barcelona, Spain

15. Centro Integral Oncológico Clara Campal, Madrid, Spain

16. University Hospitals Leuven, Leuven, Belgium

17. Prince of Wales Hospital, Sydney, Australia

18. Celgene Corporation, Summit, NJ

19. Bionomics Ltd., Thebarton, Australia

Abstract

4005^ Background: nab-paclitaxel (nab-P; 130 nm albumin-bound paclitaxel) has demonstrated both single-agent activity and synergy with gemcitabine (G) in preclinical models of pancreatic cancer (PC). nab-P + G also demonstrated promising efficacy in a phase I/II study in metastatic PC (J Clin Oncol. 2011:4548-4554), warranting a phase III study of nab-P + G vs G for metastatic PC. Methods: 861 patients (pts) with metastatic PC and a Karnofsky performance status (KPS) ≥ 70 were randomized at 151 community and academic centers 1:1 to receive nab-P 125 mg/m2 + G 1000 mg/m2 days 1, 8, and 15 every 4 weeks or G alone 1000 mg/m2weekly for 7 weeks followed by 1 week of rest (cycle 1) and then days 1, 8, and 15 every 4 weeks (cycle ≥ 2). The primary endpoint was OS; secondary endpoints were PFS and ORR by independent review. Results: The median age was 63 years (range 27 - 88). KPS was 100 (16%), 90 (44%), 80 (32%), and 70 (7%). Pts had advanced disease with liver metastases (84%), ≥ 3 metastatic sites (46%), and CA19-9 ≥ 59 × ULN (46%). nab-P + G was superior to G for all efficacy endpoints: median OS was 8.5 vs. 6.7 mo (HR 0.72; 95% CI, 0.617 - 0.835; P = 0.000015); median PFS was 5.5 vs. 3.7 mo (HR 0.69; 95% CI, 0.581 - 0.821; P = 0.000024), and ORR was 23% vs. 7% (P = 1.1 × 10−10) by RECIST v1.0. Metabolic response by PET in 257 patients was 63% for nab-P + G vs 38% for G (P = 0.000051). CA19-9 response (≥ 90% decrease) was 31% for nab-P + G vs. 14% for G (P < 0.0001). Grade ≥ 3 AEs with nab-P + G vs. G included neutropenia (38% vs. 27%), fatigue (17 % vs. 7%), diarrhea (6% vs 1%), and febrile neutropenia (3% vs. 1%). Grade ≥ 3 peripheral neuropathy (PN) occurred in 17% vs. 1% of pts who received nab-P + G vs. G, respectively; for nab-P + G, PN improved to grade ≤ 1 in a median 29 days, and 44% of patients resumed nab-P treatment. The median duration of treatment was 3.9 mo for nab-P + G and 2.8 mo for G. Conclusions: MPACT was a large, international study performed at community and academic centers. nab-P + G was superior to G across all efficacy endpoints, had an acceptable toxicity profile, and is a new standard for the treatment of metastatic PC that could become the backbone for new regimens. Clinical trial information: NCT00844649.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3