Download the ESMO 2012 Abstract Book - Oxford Journals

Annals of Oncology
Results: SA #1 (Table) showed significant improvement in PFS with
aflibercept-FOLFIRI compared to placebo-FOLFIRI (P < 0.00001), thus confirming
primary PFS analysis. SA #2 also showed an improvement in PFS with aflibercept vs
placebo; difference was not significant (P = 0.0017) at the 0.0001 α level.
Discrepancies between IRC and investigators’ assessments were noted in placebo (n
= 273, 45.8%) and aflibercept (n = 231, 39.3%) arms. An unstratified log-rank test
comparing primary PFS in the two arms was consistent with the stratified analysis,
showing a significant difference in PFS with aflibercept (P = 0.00005). Aflibercept
showed typical anti-VEGF side effects.
Conclusion: The data from these PFS sensitivity analyses (SAs) are consistent with
the primary analysis of PFS in VELOUR, further supporting the statistically
significant and clinically meaningful improvement in PFS seen in the primary
analysis. Funded by Sanofi & Regeneron
Analysis: PFS
(months) Placebo N = 614 Aflibercept N = 612 HR [99.99% CI]
Primary: 4.67 4.07 – 5.55 6.90 5.88 – 7.85 0.758 [0.578 – 0.995]
SA #1: 4.53 4.07 – 5.68 6.97 6.05 – 8.51 0.654 [0.477 – 0.895]
SA #2: 4.50 4.04 – 5.55 6.24 5.49 – 7.19 0.814 [0.630 – 1.052]
Disclosure: E. Van Cutsem: I have received research funding from Sanofi.
J. Tabernero: I have an advisory relationship with sanofi, for which I have been
compensated. R. Lakomy: I have received research funding from Sanofi. P. Ruff: I
have received honorarium from Amgen, Merck AG, Roche, Sanofi and Pfizer. I have
received research funding from Amgen, Merck AG, Sanofi and Pfizer. I have received
travel grants from Amgen, Roche, and Pfizer. D. Ferry: I have an advisory
relationship with Sanofi. I have received honorarium from Sanofi. E. Boelle: I am an
employee of Sanofi. C. Allegra: I have an advisory relationship with Sanofi. All other
authors have declared no conflicts of interest.
582P A PHASE II STUDY OF COMBINED CETUXIMAB, IRINOTECAN,
OXALIPLATIN AND UFT (ESCOUT) IN PATIENTS WITH
ADVANCED COLORECTAL CANCER (ACRC) INCORPORATING
ANALYSIS OF CIRCULATING TUMOUR CELLS (CTCS)
M. Krebs 1 , S. Gollins 2 , I. Chau 3 , J. Hasan 4 , M. Braun 4 , K. Morris 1 , J. Beech 4 ,
G. Adaway 4 , C. Dive 1 , M.P. Saunders 4
1 Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer
Research, Manchester, UNITED KINGDOM, 2 Clinical Oncology, North Wales
Cancer Treatment Centre, Wales, UNITED KINGDOM, 3 Medicine, Royal Marsden
Hospital, Sutton, UNITED KINGDOM, 4 Medical Oncology, The Christie NHS
Foundation Trust, Manchester, UNITED KINGDOM
Introduction: Patients (pts) with ≥3 CTCs/7.5ml blood at baseline, enumerated by
the CellSearch® (Veridex) system, have poor overall survival (OS)1. CTC guided
treatment strategies may improve pt outcomes. This study investigated the efficacy of
combining 4 active agents and evaluated CTC numbers for prognostic and
pharmacodynamic utility.
Methods: Pts with previously untreated, inoperable, ACRC and wtKRAS were
eligible. Chemotherapy was administered every 28 days with Cetuximab 400 mg/m 2
D1 & D15 and UFT 250 mg/m 2 with calcium folinate 30mg TDS D1-21. UFT dose
was reduced by 1 caps/day for grade 2/3 diarrhoea. Irinotecan 180 mg/m 2 D1 and
oxaliplatin 100 mg/m 2 D15 alternated to reduce long-term toxicity of each drug.
Treatment was continued until disease progression. The primary end-point was
response rate (RR) and secondary endpoints included progression free survival (PFS),
OS, toxicity and CTC number. Blood samples (7.5ml) for CTC analysis were drawn
at baseline and D15. CTCs were enumerated using the CellSearch® system. Results:
Forty-eight pts were recruited; 46 were evaluable for response and 42 for CTC
enumeration. A 67% RR was achieved with disease control in 91% - CR 2 pts (4%),
PR 29 (63%) & SD in 11pts (24%). Two pts with inoperable colonic tumours had
curative resections after chemotherapy; no patients had liver only disease. Grade 3
toxicities included diarrhoea (21%), lethargy (17%), neutropenia (8%), parasthesia
(17% G2, no G3) and alopecia (4% G2). Only 14 pts have died so OS is expected to
increase with longer review. At baseline 50% pts had ≥3 CTCs suggesting this cohort
comprised a poor prognostic group; median PFS/OS of these pts was 8.5/18.8
months(m), considerably better than expected (cf 6.1/11.6m in Cohen1). Pts with 5 Ug/L
(primary tumor is a “secretor”) whilst 50.5% did not have elevated pre-op CEA
(“non-secretor”). The pre-op CEA value is prognostic (continuous variable, p <
0.01). During follow-up, all non-secretors and 58% of secretors achieved a trough
CEA < 5 Ug/L. Achieving a trough CEA 5 Ug/
L prior to relapse was observed in 51% of all patients. This new rise was more
likely to be observed among patients whose initial primary was secretory (p <
0.01). The median time from new rise in CEA to clinical relapse was 2.4 months.
This was not different between initial secretors and non-secretors. At clinical
relapse, 82% of initial secretors vs 47% of initial non-secretors had elevated CEA
(p < 0.01).
Conclusions: Pre-operative CEA levels prior to initial surgery influence CEA
dynamics post curative resection in patients with recurrent colorectal cancer. Among
secretors, fall to baseline CEA is associated with longer time to recurrence. Among
all patients, a new rise in CEA is more likely to occur in patients whose initial
primary is secretory. Once this new rise occurs, median time to recurrence is 2.4
months and this duration is not dependent on initial secretory status.
Disclosure: All authors have declared no conflicts of interest.
584P FDG-PET TUMOR LOAD PARAMETERS MEASURED BY TOTAL
LESION GLYCOLYSIS AS PREDICTORS OF TREATMENT
RESPONSE AND OUTCOME IN METASTATIC COLORECTAL
CANCER
H. El Mansy 1 , C. Garcia 2 , A. Deleporte 1 , L. Ameye 3 , A. Hendlisz 1 , P. Flamen 2
1 Medical Oncology, Institut Jules Bordet, Brussels, BELGIUM, 2 Nuclear
Medicine, Institut Jules Bordet, Brussels, BELGIUM, 3 Data Centre, Institute Jules
Bordet, Brussels, BELGIUM
Objectives: Early metabolic response measured by the change of FDG maximum
Standardized Uptake Value (SUVmax) on PET-CT after 1 cycle of chemotherapy in
patients with metastatic colorectal cancer (mCRC) can predict negative objective
response and is correlated to Overall Survival (OS) (Hendlisz et al. 2011). The aim of
this work is to assess the correlation between the change in FDG-PET whole body
metabolic tumoral load parameters and the RECIST response, progression free
survival (PFS), OS.
Methods: FDG-PET/CT scans were performed at baseline and on Day 14, in 41
patients with unresectable mCRC undergoing a biweekly chemotherapy regimen.
Patients were followed-up for up to 28 months. The change in Functional Tumor
Volume (FTV) and Total Lesion Glycolysis (TLG) (TLG = FTV x SUVmean) of all
the lesions was calculated using a fixed threshold segmentation algorithm (threshold
for segmentation = SUV mean of 30 mm sphere in the right lobe of the liver plus 3
standard deviations) corrected to lean body mass (Wahl et al 2009). Predictive and
prognostic value was tested through correlation with RECIST response (using
independent dedicated CT), PFS and OS. A cutoff value for TLG responding patients
was set at 40% or more decrease in the baseline value.
Results: 39 patients were evaluable for analysis. The median OS was 20 months (95%
CI, 10 to 28), the change in whole body FTV and TLG were significantly related to
RECIST response (p-value: 0.015 and 0.0038), to PFS (P-value: 0.009, 0.018) and to
OS (p-value: 0.002, 0.0027). Patients with > 40% decrease in TLG have better PFS:
median 12 months compared to median 3 months in the rest of the patients [log
rank test p-value 0.004; HR 0.31 (95% CI, 0.14 to 0.72)], and a better median OS 27
months compared to 11 months [log rank test p-value 0.05; HR 0.38 (95% CI, 0.14
to 1.04)].
Conclusions: Changes in the metabolic tumoral load parameters after one cycle of
standard chemotherapy for mCRC are predictors of RECIST response, progression
free and overall survival.
Disclosure: All authors have declared no conflicts of interest.
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds397 | ix199