558P - Understanding the value of response and early tumour shrinkage (ETS) in pts with WT KRAS mCRC treated with panitumumab (P) plus FOLFOX (F)

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Biomarkers
Colon Cancer
Rectal Cancer
Presenter Jean-Yves Douillard
Authors J. Douillard1, S. Siena2, J. Tabernero3, M. Peeters4, C. Davison5, S. Braun6, R. Sidhu7
  • 1Medical Oncology, Centre René Gauducheau (ICO) Institut de Cancerologie de l'Ouest, 44805 - Nantes/FR
  • 2Department Of Medical Oncology, Ospedale Niguarda Ca’ Granda, Milan/IT
  • 3Oncology Department, Vall d'Hebron University HospitalMedical Oncology Service, ES-08035 - Barcelona/ES
  • 4Department Of Medical Oncology, University Hospital Antwerp, Antwerp/BE
  • 5Biostatistics, Amgen Ltd., Uxbridge/UK
  • 6Medical Development, Amgen (Europe) GmbH, Zug/CH
  • 7Medical Development, Amgen Inc., Thousand Oaks/US



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.


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.


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 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.


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
<30% ≥30% <30% ≥30%
ITT (N = 584) N = 186 (62%) N = 112 (38%) N = 141 (49%) N = 145 (51%)
Median OS months 17.6 29.5 18.0 30.3
[95% CI] [15.4-20.2] [22.5-34.5] [14.2-21.7] [26.6-36.8]
HR 0.543 0.540
[95% CI] [0.404-0.730] [0.404-0.722]
p-value <0.0001 <0.0001
Median PFS months 7.3 9.6 7.4 11.1
[95% CI] [5.8-8.7] [7.7-10.8] [6.2-9.2] [9.6-13.0]
HR 0.648 0.617
[95% CI] [0.500-0.839] [0.478-0.796]
p-value 0.0010 0.0002
<20% ≥20% <20% ≥20%
ITT (N = 584) N = 130 (44%) N = 168 (56%) N = 87 (30%) N = 199 (70%)
Median OS months 16.6 25.1 10.7 30.2
[95% CI] [12.4-18.8] [22.1-32.8] [9.4-16.1] [27.4-33.1]
HR 0.519 0.431
[95% CI] [0.394-0.683] [0.320-0.582]
p-value <0.0001 <0.0001
Median PFS months 5.7 9.3 5.7 11.0
[95% CI] [5.3-7.6] [7.7-9.9] [4.0-7.1] [9.6-12.8]
HR 0.624 0.462
[95% CI] [0.487-0.799] [0.350-0.609]
p-value 0.0002 <0.0001


S. Siena: Advisory role for Amgen, AstraZeneca, Merck Serono, Roche, Celgene.

J. Tabernero: Honoraria for consultancy/ advisory boards from Merck-Serono, Amgen, Roche, MSD, Onyx, Bayer, Sanofi-Aventis and Novartis.

J. Douillard: Advisory role: Amgen, sanofi-aventis,Merck Serono; Honoraria: Amgen, Sanofi-aventis.

M. Peeters: Consultant/advisory role for Amgen and also received honoraria and research funding.

C. Davison: Employee of Amgen and holds Amgen stock.

S. Braun: Employee of Amgen and holds Amgen stock.

R. Sidhu: Employee of Amgen and hold Amgen stock.