623PD - A phase I and randomized phase II trial to evaluate the efficacy and safety of nab-paclitaxel (nab-P) in combination with gemcitabine (G) for the t...

Date 11 September 2017
Event ESMO 2017 Congress
Session Gastrointestinal tumours, non-colorectal
Topics Anti-Cancer Agents & Biologic Therapy
Pancreatic Cancer
Gastrointestinal Cancers
Presenter Manuel Hidalgo
Citation Annals of Oncology (2017) 28 (suppl_5): v209-v268. 10.1093/annonc/mdx369
Authors M. Hidalgo1, R. Pazo-Cid2, C. Guillen-Ponce3, R. López4, R. Vera5, M. Reboredo6, A. Muñoz7, E. Martinez de Castro8, R. Díaz Beveridge9, A. La Casta10, J.I. Martin-Valades11, A. Cubillo12, J. Martínez-Galán13, I. Ales14, J. Sastre15, T. Macarulla Mercade16
  • 1Medical Oncology Department, Beth Israel Deaconess Medical Center,, MA 02215 - Boston/ES
  • 2Medical Oncology Department, Miguel Servet University Hospital, Zaragoza/ES
  • 3Medical Oncology Department, Hospital Universitario Ramon y Cajal, 28031 - Madrid/ES
  • 4Medical Oncology Department, HOSPITAL CLINICO DE SANTIAGO, Santiago de Compostela/ES
  • 5Medical Oncology, Hospital de Navarra, 31008 - Pamplona/ES
  • 6Medical Oncology Department, Hospital Universitario a Coruna - a Coruna, 15006 - A Coruna/ES
  • 7Medical Oncology Department, Hospital General Universitario Gregorio Marañon, Madrid/ES
  • 8Medical Oncology, Hospital Universitario Marques de Valdecilla, 39008 - Santander/ES
  • 9Medical Oncology, Hospital Universitari i Politècnic La Fe, 46026 - Valencia/ES
  • 10Medical Oncology Department, Hospital Universitario Donostia, Donostia/ES
  • 11Medical Oncology Department, Hospital Universitario Fundación Jiménez Díaz, Madrid/ES
  • 12Medical Oncology Department, Hospital Madrid Norte San Chinarro Centro Integral Oncologico Clara Campal, 28050 - Madrid/ES
  • 13Medical Oncology Department, Hospital Universitario Virgen de las Nieves, Granada/ES
  • 14Medical Oncology Department, Hospital Universitario Carlos Haya, Málaga/ES
  • 15Medical Oncology Department, Hospital Clinico Universitario San Carlos, 28040 - Madrid/ES
  • 16Medical Oncology Department, Vall d`Hebron Institute of Oncology (VHIO)-Cellex Center, 08035 - Barcelona/ES

Abstract

Background

Nab-P+G significantly improved overall survival versus G in Patients (P) with Karnofsky index ≥70% metastatic PDAC (Von Hoff et al, 2013). The aim of this study was to select a tolerable dose -schedule of nab-P+G (Ph I), and to evaluate the efficacy of the selected regimen (Ph II) in patients with previously untreated ECOG-2 advanced PDAC.

Methods

In the phase1 portion of the study patients were randomized to one of 4 treatment regimens including G 1000 mg/m2 and nab-P 150 mg/m2 (arm B) or 125 mg/m2 (arm D) days 1 and 15 every 28 days or same dose of G and nab-P 100 mg/m2 (arm C) or 125 mg/m2 (arm E) days 1, 8, and 15 every 28 days. The two safest regimens determined by analyzing hematological and non-hematological grade 3-4 toxicity, 30 and 60 days mortality, treatment discontinuation due to toxicity and dose intensity were selected for evaluation in the phase 2 portion of the study with 6 months overall survival (OS) as the primary endpoint.

Results

Regimens arm C and arm E (days 1, 8, 15 every 28 days schedule) were selected for the phase 2 portion of the study. A total of 221 patients (111 in arm C/110 in arm E) were enrolled. Median age was 71/68 y, 51/55% were male and 91/83% had metastatic disease (liver 63/62%). Most frequent grade 3-4 toxicity per arm were anemia (12/7%), neutropenia (32/30%), thrombocytopenia (7/11%), febrile neutropenia (3/4%), asthenia (14/16%) and neurotoxicity (11/16%). There were no significant differences in 6 months OS 63/69%, response rate (RR) 24/28% and median progression free survival (PFS) 5.7/6.7 months respectively in each arm.

Conclusions

Nab-P in combination with G, both at 100 and 125 mg/m2 dose administered on a standard schedule of days 1, 8 and 15 is well tolerated and results in acceptable OS, RR and PFS in this fragile patient population.

Clinical trial identification

NCT02382263 EudraCT: 2012-003605-97

Legal entity responsible for the study

PH Research

Funding

Celgene

Disclosure

M. Hidalgo: Honoraria: Celgene. Consulting or advisory role: Celgene. Research funding: Celgene. Travel, accomodations: Celgene. R. Pazo-Cid: Consulting or advisory role: Celgene, Baxalta. A. Muñoz: Consulting or advisory role: Celgene. J. Sastre: Consulting or advisory role: Amgen, Sanofi, Bayer, Boheringer. Travel accomodations: Merck. Researcha funding: Amgen, Merck. All other authors have declared no conflicts of interest.