Department of Medicine, Division of Hematology, Oncology, and Tumor Immunology (CCM), Charité Universitaetsmedizin Berlin, Berlin, Germany
Jobst C. von Einem , Sebastian Stintzing , Ludwig Fischer von Weikersthal , Thomas Decker , Alexander Kiani , Ursula Vehling-Kaiser , Salah-Eddin Al-Batran , Tobias Heintges , Christian A. Lerchenmuller , Christoph Kahl , Gernot Seipelt , Martina Stauch , Werner Scheithauer , Joerg Hielscher , Michael Scholz , Dominik Paul Modest , Andreas Jung , Thomas Kirchner , Volker Heinemann
Background: The FIRE-3 study (AIO KRK-0306) was designed as a randomized multicenter trial to compare the efficacy of FOLFIRI plus cetuximab (cet) to FOLFIRI plus bevacizumab (bev) as first-line treatment in KRAS WT mCRC patients. FOLFIRI plus cet as first-line treatment of KRAS WT mCRC patients resulted in comparable overall response rates (ORR) and progression free survival (PFS) when compared to FOLFIRI plus bev. Overall survival (OS) was significantly longer in the FOLFIRI plus cet arm. Methods: In the present analysis of the FIRE-3 trial we explored the impact of primary tumor resection on outcome in relation to anti-EGFR vs. anti-VEGF treatment. Furthermore, we investigated the prognostic value of synchronous versus metachronous metastases. Results: In patients with synchronous disease no significant difference in OS was detected when comparing resected (n=339) vs. non-resected (n=97) patients (p-value: 0.29, HR: 1.17, 95%-CI: 0.88 – 1.55). In the cetuximab arm, resection (n=167) showed no significant benefit in OS when compared to non-resection (n=52) (p-value: 0.51, HR: 1.15, 95%-CI: 0.77 – 1.71). Treated with bevacizumab, similar results were present, when comparing resection (n=172) vs. non-resection (n=45); (p-value: 0.29, HR: 1.25, 95%-CI: 0.83 – 1.9). A strong trend was seen when comparing OS in treatment arms cet. (n=219) vs. bev. (n=217)) for patients with synchronous disease; (p-value: 0.05, HR: 1,26, 95%-CI: 1.0 - 1.59). 436/592 pts suffered from synchronous, 153/592 from metachronous disease (in 3/592 pts the information was not given). Median OS in pts with synchronous disease was 24.5 months and 29.5 in pts with metachronous disease (p-value: 0.02, HR: 0.76, 95%-CI: 0.6 - 0.96). In pts treated in the cetuximab arm metachronous disease (n=77) was associated with a trend towards longer OS when compared to synchronous disease (n= 219) (p-value: 0.13, HR: 0.76, 95%-CI: 0.54 – 1.1). The same effect was present in the bevacizumab arm (p-value: 0.05, HR: 0.73, 95%-CI 0.53 – 1.0) when comparing pts with synchronous disease (n=217) vs. pts. with metachronous disease (n=76). Conclusions: In the FIRE-3 study, metachronous disease was associated with superior OS compared to synchronous disease. This finding was accentuated in the bevacizumab arm. The role of resection of the primary tumor had no impact on survival. Clinical trial information: NCT00433927.
Disclaimer
This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Abstract Disclosures
2024 ASCO Gastrointestinal Cancers Symposium
First Author: Karam Ashouri
2023 ASCO Annual Meeting
First Author: Nicola Normanno
2024 ASCO Gastrointestinal Cancers Symposium
First Author: Julian Walter Holch
2022 ASCO Annual Meeting
First Author: Zhichao Jiang