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
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.
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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