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experienced significantly more ≥ grade 2 neurotoxicity (51.2% vs. 12.5%, P = 0.001)
(Table-1). Neurotropin was the only factor that affected the incidence of ≥ grade 2
neurotoxicity in the Kaplan-Meier log rank and the multivariate Cox proportional
hazards regression analysis.
Conclusion: Neurotropin combined with oxaliplatin decreases chronic neurotoxicity
effectively and safely.
Disclosure: All authors have declared no conflicts of interest.
557P A RANDOMIZED, CONTROLLED TRIAL OF CETUXIMAB PLUS
CHEMOTHERAPY FOR PATIENTS WITH KRAS WILD-TYPE
UNRESECTABLE COLORECTAL LIVER-LIMITED METASTASES
J. Xu, L. Ye, L. Ren, Y. Wei
Department of General Surgery, Zhongshan Hospital Fudan University,
Shanghai, CHINA
Background: To assess the effect of cetuximab combined with chemotherapy in
first-line treatment for unresectable colorectal liver metastases (CLM).
Methods: After resection of the primary focus, patients (pts) with non-resectable
synchronous liver-limited metastases from wild-type KRAS colorectal cancer were
randomly assigned to received chemotherapy (FOLFIRI or mFOLFOX6) plus
cetuximab (arm A) or chemotherapy alone (arm B). The primary end point was the
rate of secondary resection for liver metastases. Secondary end points included tumor
response and survival.
Results: From June 2008 to December 2011, 116 pts were eligible (59 in arm A and
57 in arm B). The 3-year overall survival (OS) rate and median survival time (MST)
of the total pts was 32% and 27.5 months (mo), respectively. R0 resection rate for
liver metastases was 30.5% (18/59) in arm A and 8.8% (5/57) in arm B, with
significant difference (Odds ratio = 4.57, p< .01). In R0 resected 18 pts from arm A,
the median disease free survival and MST was 11.4 and 46.6 mo. The pts in arm A
had improved objective response (OR, 66.1% v 33.3%, Odds ratio = 3.90, p< .01),
increased 3-year OS rate (43% v 21%, p= .01) and prolonged MST (32.8 v 22.8 mo,
HR =0.49, p= .01) compared with those in arm B. Furthermore, for the pts without
liver surgery, people from arm A also got more survival benefit than those from arm
B on 3-year OS rate (25% v 17%, p= .047), MST (28.2 v 21.2 mo, HR =0.55, p= .047)
and progressives free survival (8.3 v 5.2 mo, HR =0.64, p= .03). In addition, in arm
A, pts who experienced resection of liver metastases were significantly improved
3-year OS rate (74% v 25%, p= .02) and MST (46.6 v 28.2 mo, HR = 0.29, p= .02)
than those without liver surgery, and the pts harboring BRAF wild-type tumors
gained more benefit on MST (35.8 v 23.4 mo, HR =0.39, p= .045) rather than on OR
( 70.0% v 44.4%, Odds ratio = 2.92, p > .05), when compared to those with mutated
BRAF tumors.
Conclusion: For initially unresectable CLM population with KRAS wild-type,
cetuximab combined with chemotherapy could improve resectability of liver
metastases, response rates and survival compared with chemotherapy alone
(ClinicalTrials.gov number NCT01564810).
Disclosure: All authors have declared no conflicts of interest.
558P UNDERSTANDING THE VALUE OF RESPONSE AND EARLY
TUMOUR SHRINKAGE (ETS) IN PTS WITH WT KRAS MCRC
TREATED WITH PANITUMUMAB (P) PLUS FOLFOX (F)
J. Douillard 1 , S. Siena 2 , J. Tabernero 3 , M. Peeters 4 , C. Davison 5 , S. Braun 6 ,
R. Sidhu 7
1 Medical Oncology, Centre René Gauducheau (ICO) Institut de Cancerologie de
l’Ouest, Nantes, FRANCE, 2 Department of Medical Oncology, Ospedale
Niguarda Ca’ Granda, Milan, ITALY, 3 Oncology Department, Vall d’Hebron
University HospitalMedical Oncology Service, Barcelona, SPAIN, 4 Department Of
Medical Oncology, University Hospital Antwerp, Antwerp, BELGIUM,
5 Biostatistics, Amgen Ltd., Uxbridge, UNITED KINGDOM, 6 Medical
Development, Amgen (Europe) GmbH, Zug, SWITZERLAND, 7 Medical
Development, Amgen Inc., Thousand Oaks, UNITED STATES OF AMERICA
Introduction: In clinical trials, tumour response is considered clinically
meaningful when a lesion shrinks by ≥30%, according to RECIST (ORR). It
has been purported that in pts with WT KRAS mCRC treated with an
anti-EGFR mAb, both ORR and ETS (week 8 [W8]; ≥20%) predict improved
OS compared with standard treatment. We explore the validity of these
hypotheses.
Methods: Using final analysis data from PRIME, we calculated median OS and PFS
in pts with WT KRAS mCRC who did or did not achieve: a RECIST response (≥/<
30%); or ETS (≥/ < 20%) at W8. We calculated the binary correlation coefficients
(Phi) for the association between meeting the above shrinkage criteria at W8 (yes/
no) and OS at 2 years.
Results: Consistent with the previously published finding that ORR is higher with P
+ F vs F, at W8 more pts treated with P + F (vs F) had a RECIST response (Table).
Irrespective of treatment arm, median OS and PFS were significantly longer in pts
who achieved either ETS or a RECIST response (vs pts who did not; Table). Pts
Annals of Oncology
receiving P + F (vs F) showed longer median OS and PFS in each shrinkage group.
OS trends favoured the P arm for pts achieving ETS (vs F alone; Table). However,
outcomes were similar between arms in pts that achieved a RECIST response at W8.
The correlation coefficients between meeting the ≥30% or ≥20% criterion and OS at
2 years were 0.21 and 0.27, respectively.
Conclusions: Regardless of treatment arm, pts achieving a RECIST response
(≥30%) or ETS (≥20%) at W8 demonstrated improved PFS and OS compared
with those who did not. Trends toward longer OS were observed in pts treated
with P + F achieving ETS compared with F alone. Potential imbalances in
post-protocol anti-EGFR mAb use and resection rate limit the interpretation of
ORR in predicting OS. The poor Phi values found in PRIME between W8
tumour shrinkage and 2-year OS suggest that ORR and ETS alone in the
first-line treatment of mCRC are inappropriate surrogates for predicting OS.
FOLFOX Panitumumab + FOLFOX