Cetuximab and chemotherapy in the treatment of patients with initially “nonresectable” colorectal (CRC) liver metastases: Long-term follow-up of the CELIM trial.

Authors

null

Gunnar Folprecht

University Hospital Carl Gustav Carus, University Cancer Center / Medical Department I, Dresden, Germany

Gunnar Folprecht , Thomas Gruenberger , Wolf Bechstein , Hans-Rudolf Raab , Juergen Weitz , Florian Lordick , Joerg Thomas Hartmann , Hauke Lang , Tanja Trarbach , Jan Stoehlmacher-Williams , Torsten Liersch , Detlev Ockert , Dirk Jaeger , Ulrich Steger , Thomas Suedhoff , Claus-Henning Kohne

Organizations

University Hospital Carl Gustav Carus, University Cancer Center / Medical Department I, Dresden, Germany, Department of General Surgery, Medical University of Vienna, Vienna, Austria, Goethe University Hospital, Frankfurt, Germany, Klinikum Oldenburg, Oldenburg, Germany, University Hospital Carl Gustav Carus, University Cancer Center / Surgical Department, Dresden, Germany, Universitätsklinikum Leipzig, Universitäres Krebszentrum (UCCL), Leipzig, Germany, Kiel University Hospital, Kiel, Germany, Universitätsmedizin Mainz, Mainz, Germany, West German Cancer Center, Department of Medical Oncology, University Duisburg-Essen, Essen, Germany, Department of General and Visceral Surgery, University Medical Center, Georg-August-University, Göttingen, Germany, Krankenhaus der Barmherzigen Brüder, Trier, Germany, National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany, Chirurgische Klinik und Poliklinik I, University of Wuerzburg, Wuerzburg, Germany, Klinikum Passau, Passau, Germany, Onkologie Klinikum Oldenburg, Oldenburg, Germany

Research Funding

Pharmaceutical/Biotech Company

Background: CRC liver metastases can be resected after downsizing with intensive chemotherapy schedules, with a strong correlation between the response and resection rates. Cetuximab plus chemotherapy has been shown to increase the rates of tumor response and resection of liver metastases. (Van Cutsem et al, JCO 2011). Methods: Patients (pts) with technically non-resectable and/or with > 4 liver metastases were randomized to treatment with FOLFOX/cetuximab (arm A) or FOLFIRI/cetuximab (arm B) and evaluated regarding resectability every 2 months. Resection was offered to all patients who became resectable during the study. K-ras and b-raf status were retrospectively evaluated. Data on tumor response and resection were reported earlier (Folprecht et al, Lancet Oncol 2010). Overall and progression free survival were analyzed in December 2012. Results: Between Dec 2004 and March 2008, 56 pts were randomized to arm A, 55 to arm B. For the current analysis, 109 pts were evaluable for overall survival (OS), and 106 patients for PFS. The median OS was 35.7 [95% CI: 27.2-44.2] months (arm A: 35.8 [28.1-43.6], arm B: 29.0 [16.0-41.9], HR 1.03 [0.66-1.61], p=0.9). The median PFS was 10.8 [9.3-12.2] months (Arm A: 11.2 [7.2-15.3], Arm B: 10.5 [8.9-12.2], HR 1.18 [0.79-1.74], p=0.4). Patients with R0 resection had a better OS (median: 53.9 [35.9-71.9] mo) than patients without R0 resection (27.3 [21.1-33.4] mo, p=0.002) and a better PFS (median 15.4 [11.4-19.5] and 8.9 [6.7-11.1] mo in R0 resected and not R0 resected pts, p<0.001). The 5 year survival in R0 resected patients is 46.2% [29.5-62.9%]. Conclusions: This study confirmed a favourable long term survival of patients with initially “nonresectable” CRC liver metastases treated in a multidisciplinary approach of neoadjuvant chemotherapy with cetuximab and subsequent metastasectomy in pts who became resectable. Clinical trial information: NCT00153998.

Estimated OS and PFS.
OS SO N 1y 2y 3y 4y 5y
OS All pts 109 90% 62% 48% 34% 28%
K-RAS wt 69 88% 68% 53% 40% 33%
Arm A 54 89% 63% 49% 35% 28%
Arm B 55 91% 62% 47% 34% 28%
R0 resected 36 89% 78% 64% 53% 46%
No R0 resection 70 91% 54% 39% 24% 19%
PFS All pts 106 43% 15% 6% 5% 5%
K-RAS wt 67 49% 18% 6% 5% 5%
R0 resected 36 69% 25% 11% 8% 8%

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Abstract Details

Meeting

2013 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Gastrointestinal (Colorectal) Cancer

Track

Gastrointestinal Cancer—Colorectal and Anal

Sub Track

Colorectal Cancer

Clinical Trial Registration Number

NCT00153998

Citation

J Clin Oncol 31, 2013 (suppl; abstr 3538)

DOI

10.1200/jco.2013.31.15_suppl.3538

Abstract #

3538

Poster Bd #

1D

Abstract Disclosures