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gastrointestinal tumors, non-colorectal
666O TH-302 + GEMCITABINE (G + T) VS GEMCITABINE (G) IN
PATIENTS WITH PREVIOUSLY UNTREATED ADVANCED
PANCREATIC CANCER (PAC)
M. Borad 1 , S. Reddy 2 , N. Bahary 3 , H. Uronis 4 , D.S. Sigal 5 , A.L. Cohn 6 ,
W. Schelman 7 , J. Stephenson 8 , C. Eng 9 , D.P. Ryan 10
1 Oncology, Mayo Clinic Cancer Center - Arizona, Scottsdale, AZ, UNITED
STATES OF AMERICA, 2 Oncology, Louisiana State University Health Sciences
Center, Shreveport, LA, UNITED STATES OF AMERICA, 3 Oncology, University of
Pittsburgh Medical Center, Pittsburgh, PA, UNITED STATES OF AMERICA,
4 Oncology, Duke University, Durham, NC, UNITED STATES OF AMERICA,
5 Oncology, Scripps Clinical Medical Group, La Jolla, CA, UNITED STATES OF
AMERICA, 6 Oncology, Rocky Mountain Cancer Centers, Denver, CO, UNITED
STATES OF AMERICA, 7 Oncology, University of Wisconsin, Madison, WI,
UNITED STATES OF AMERICA, 8 Oncology, Institute for Translational Oncology
Research, Greenville, SC, UNITED STATES OF AMERICA, 9 Clinical Operations,
Threshold Pharmaceuticals, South San Francisco, CA, UNITED STATES OF
AMERICA, 10 Oncology, Massachusetts General Hospital, Boston, MA, UNITED
STATES OF AMERICA
Background: TH-302 is a hypoxia targeted prodrug with a hypoxia-triggered
2-nitroimidazole component designed to release the DNA alkylator,
bromo-isophosphoramide mustard (Br-IPM), when reduced in severe hypoxia. A
randomized Phase 2B study (NCT01144455) was conducted to assess the benefit of
G + T to standard dose G as first-line therapy of PAC.
Materials and methods: An open-label multi-center study of two dose levels of
TH-302 (240 mg/m 2 or 340 mg/m 2 ) in combination with G versus G alone
(randomized 1:1:1). G (1000 mg/m 2 ) and T were administered IV over 30-60 minutes
on Days 1, 8 and 15 of a 28-day cycle. Patients on the G could crossover after
progression and be randomized to a G + T arm. The primary efficacy endpoint was a
comparison of progression-free survival (PFS) between the combination arms and G
alone (80% power to detect 50% improvement in PFS with one-sided alpha of 10%).
Summary PFS outcome has previously been reported; more detailed PFS as well as
the initial overall survival (OS) data are presented.
Results: 214 pts were treated; 164 (77%) Stage IV and 50 (23%) Stage IIIB. Median
age 65 (range 29-86); 126 M/88 F; 40% ECOG 0/60% ECOG 1. Receiving 6 or
more cycles: 32% G; 45% G + T240; 55% G + T340. Median PFS was 3.6 mo in G
vs 5.5 mo in G + T240 (p = 0.031) and 6.0 mo in G + T340 (p = 0.008). Poorer
prognostic factors (older age, poorer performance status, reduced albumin) were
associated with larger treatment effect. Median OS was 7.0 mo in G vs 9.0 in G +
T240 and 9.5 mo in G + T340. RECIST best response was 12% in G vs 17% in G +
T240 and 27% in G + T340. CA19-9 decreases were significantly greater G + T340.
A >50% CA19-9 decrease was 52% with G vs 50% with G + T240 and 70% with G
+ T340. AEs leading to discontinuation were: 16% G, 15% G + T240 and 11% G +
T340. Rash (45% in G + T340) and stomatitis (36% in G + T340) were greater in
combination, 4 pts Grade 3 rash. Grd 3/4 thrombocytopenia were 11% G, 39% G
+ T240 and 59% G + T340 and Grd 3/4 neutropenia were 28% G, 56% G + T240
and 59% G + T340.
Conclusions: The combination of G plus TH-302 improved the efficacy of G. A
TH-302 dose of 340 mg2 was identified for future studies. Skin and mucosal toxicity
and myelosuppression were the most common TH-302 related AEs with no increase
in treatment discontinuation.
Disclosure: All authors have declared no conflicts of interest.
Annals of Oncology 23 (Supplement 9): ix224–ix257, 2012
doi:10.1093/annonc/mds398
667PD A RANDOMISED MULTICENTRE TRIAL OF EPIRUBICIN,
OXALIPLATIN AND CAPECITABINE (EOC) + PANITUMUMAB
IN ADVANCED OESOPHAGO-GASTRIC CANCER (REAL3):
UPDATED RESULTS
T.S. Waddell 1 , J. Reis-Filho 2 , D. Gonzalez-De-Castro 3 , I. Chau 1 ,
A. Wotherspoon 4 , S. Gupta 5 , C. Saffery 1 , G. Middleton 6 , J. Wadsley 7 ,
D. Cunningham 1
1 Department of Medicine, Royal Marsden Hospital, Sutton, UNITED KINGDOM,
2 Department of Molecular Pathology, Institute for Cancer Research, London,
UNITED KINGDOM, 3 Department of Molecular Diagnostics, Institute for Cancer
Research, Sutton, UNITED KINGDOM, 4 Department of Histopathology, Royal
Marsden Hospital, London, UNITED KINGDOM, 5 Statistics Department, Royal
Marsden Hospital, London, UNITED KINGDOM, 6 St. Lukes Cancer Centre,
Royal Surrey County Hospital, Guildford, UNITED KINGDOM, 7 Department of
Oncology, Weston Park Hospital, Sheffield, UNITED KINGDOM
Background: EGFR overexpression occurs in 30-90% of oesophago-gastric
adenocarcinomas (OGA), and correlates with poor prognosis. The REAL-3 trial
evaluated the addition of the anti-EGFR antibody panitumumab (P) to epirubicin,
oxaliplatin and capecitabine (EOC) in advanced OGA.
Methods: Patients with untreated, metastatic or locally advanced OGA were
randomised to EOC (E 50mg/m 2 , O 130mg/m 2 , C 1250mg/m 2 /day) or mEOC + P (E
50mg/m 2 , O 100mg/m 2 , C 1000mg/m 2 /day, P 9mg/kg). Primary endpoint was overall
survival (OS); secondary endpoints were progression-free survival (PFS), response
rate (RR), toxicity, and biomarker evaluation. Response was evaluated by RECIST
after 4 and 8 cycles.
Results: 553 patients were recruited (EOC 275, mEOC + P 278). Median OS was 11.3
months with EOC compared to 8.8 months with mEOC + P (HR 1.37: 95% CI
1.07-1.76, p = 0.013). Median PFS was 7.4 and 6.0 months respectively (HR 1.22:
95% CI 0.98-1.52, p = 0.068), with RR being 42% compared to 46% (odds ratio 1.16:
95% CI 0.81-1.57, p = 0.467). In the mEOC + P arm, OS was significantly improved
in patients with G1-3 rash (77%, n = 209) on treatment compared to those without
(23%, n = 63); median OS 10.2 vs 4.3 months (p < 0.001), with similar significant
improvements seen in RR and PFS. Multivariate analysis demonstrated a negatively
prognostic role for KRAS mutation (HR 2.1: 95% CI 1.10-4.05, p = 0.025) and
PIK3CA mutation (HR 3.2: 95% CI 1.01-10.40, p = 0.048). The above information is
being presented at ASCO 2012. Updated translational results will be available for
presentation at ESMO Congress. This will include correlation of rash with toxicity
endpoints and data relating to EGFR and KRAS amplification in this population.
Disclosure: I. Chau: I have a compensated advisory role with Roche. I have also
received honoraria and research funding from Roche. D. Cunningham: I have
received research funding from Amgen, Roche, Merck-Serono. I have undertaken
uncompensated advisory roles for Amgen and Roche. I have provided an
uncompensated expert testimony for Amgen. All other authors have declared no
conflicts of interest.
668PD NON INFERIORITY ANALYSIS OF MULTICENTER PHASE III
COMPARING CISPLATIN/S-1 (CS) WITH CISPLATIN/5-FU
(CF) AS FIRST-LINE THERAPY IN PATIENTS WITH
ADVANCED GASTRIC CANCER (FLAGS): METHODOLOGY
AND RESULTS
J.A. Ajani 1 , W. Rodriguez Pantigoso 2 , G. Bodoky 3 , V. Moiseyenko 4 ,
M. Lichinitser 5 , V.A. Gorbunova 5 , I. Vynnychenko 6 , I. Lang 3 , S. Falcon 1
1 Gastrointestinal Medical Oncology, MD Anderson, Cancer Center, Houston, TX,
UNITED STATES OF AMERICA, 2 Oncologia Y Radioterapia, Instituto de
Oncologia Y RadioterapiaClinica Rica, Clinica Vesa, Lima, PERU, 3 Department of
Oncology, St.László Hospital, Budapest, HUNGARY, 4 Medical Oncology, N.N.
Petrov Research Inst. of Oncology, St. Petersburg, RUSSIAN FEDERATION,
5 Department of Chemotherapy, N.N. Blokhin Russian Cancer Research Center,
Moscow, RUSSIAN FEDERATION, 6 Medical Oncology, Sumy Regional Oncology
Centre, Sumy, UKRAINE
Background: S-1, a new generation of oral fluoropyrimidine, is active against Advanced
Gastric Cancer (AGC). The primary analysis of FLAGS (JCO 2010; vol.28 p 1547-53)
did not show any differences in overall survival (OS) between CS and CF. S-1 has been
registered in Europe, with supportive analyses including non-inferiority (NI) analysis.
Methods: 1,053 (1,029 treated; CS = 521/CF = 508) patients (non Asian 88 + %) with
untreated, advanced gastric (83.1 %) / gastroesophageal (16.5%) adenocarcinoma
were randomized to either S-1 (25 mg/m 2 bid, d 1-21)/cisplatin (75 mg/m 2 d1)q28
© European Society for Medical Oncology 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
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