Department of Hematology and Oncology, Klinikum Großhadern and Comprehensive Cancer Center, LMU Munich, Munich, Germany
Marlies Michl , Ludwig Fischer von Weikersthal , Alexander Crispin , Thomas Decker , Alexander Kiani , Ursula Vehling-Kaiser , Salah-Eddin Al-Batran , Tobias Heintges , Christian A. Lerchenmuller , Christoph Kahl , Gernot Seipelt , Frank Kullmann , Martina Stauch , Werner Scheithauer , Joerg Hielscher , Michael Scholz , Sebastian Mueller , Dominik Paul Modest , Sebastian Stintzing , Volker Heinemann
Background: To examine the impact of tumor marker response of carcinoembryonic antigen (CEA) and carbohydrate-antigen 19-9 (CA19-9) on overall survival (OS) and progression free survival (PFS) in patients with KRAS wild-type mCRC receiving first line chemotherapy in the FIRE3-trial comparing FOLFIRI + cetuximab (cet) vs. FOLFIRI + bevacizumab (bev). Methods: Baseline tumor marker levels, the time to nadir (in days; d) and the percentage of tumor marker decrease observed at the nadir compared with baseline were analyzed. The percentage was 0 for no change and negative if the tumor marker increased. Comparisons relied on Mann-Whitney U tests for independent groups and Wilcoxon signed-rank tests for dependent ones. ROC analysis resulted in a cut-off value using the maximum of sensitivity and specificity for best response. Results: For analysis of CEA, 472/592 pts (cet arm: 230 pts; bev arm: 242 pts) were eligible and for CA19-9, 439/592 pts (cet arm: 209 pts; bev arm: 230 pts). Baseline CEA (log) and CA19-9 (log) levels both significantly correlated with OS (p=0.008 and p<0.0001, respectively), but not with PFS (p=0.26 and p=0.15, respectively). For CEA and CA19-9 median time to nadir was comparable for both study arms, however in all patients CA19-9 nadir occurred earlier than CEA nadir (p<0.0001). Extent of CEA nadir significantly differed between treatment arms (cet arm: median: 83.0%; IQR: 40.9%-94.7%; bev arm: median: 72.3%; IQR: 26.3%-91.0%; p=0.003). A similiar trend was observed for CA19-9 nadir (cet arm: median: 64.3%; IQR: 13.4%-90.7%; bev arm: 47.0%; IQR: 1.7%-86.4%; p=0.085). In univariate analysis, a CEA decrease of more than 75% correlated with longer OS (33.2 vs. 22.9 mo; p<0.0001; HR 0.63; 95%Cl: 0.50–0.80) and PFS (11.7 vs. 9.0 mo; p=0.007; HR 0.67; 95%Cl: 0.62–0.93). Conclusions: In this analysis, we demonstrate that a greater decrease of CEA during therapy correlates with longer survival and the depth of CEA decrease is significantly greater in the cetuximab-arm compared to the bevacizumab-arm. Clinical trial information: NCT00433927.
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Abstract Disclosures
2024 ASCO Gastrointestinal Cancers Symposium
First Author: Julian Walter Holch
2023 ASCO Annual Meeting
First Author: Nicola Normanno
2015 ASCO Annual Meeting
First Author: Marlies Michl
2015 Gastrointestinal Cancers Symposium
First Author: Sebastian Stintzing