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Impact of Subsequent Therapies on Outcome of the FIRE-3/AIO KRK0306 Trial: First-Line Therapy With FOLFIRI Plus Cetuximab or Bevacizumab in Patients With KRAS Wild-Type Tumors in Metastatic Colorectal Cancer
Open accessAbstract
Purpose: We investigated choice and efficacy of subsequent treatment, with special focus on second-line therapy, in the FIRE-3 trial (FOLFIRI plus cetuximab [arm A] or bevacizumab [arm B]) for patients with KRAS wild-type metastatic colorectal cancer. Patients and Methods: Start of subsequent-line (second or third) therapy was defined as use of an antitumor drug that was not part of the previous regimen. We evaluated choice, duration, and efficacy of subsequent therapy and determined the impact of subsequent-line treatment on outcome of patients in FIRE-3. Results: Of 592 patients in the intent-to-treat population, 414 (69.9%) received second-line and 256 (43.2%) received third-line therapy. In subsequent treatment lines, 47.1% of patients originally assigned to arm A received bevacizumab, and 52.2% originally assigned to arm B received either cetuximab or panitumumab. Oxaliplatin was subsequently used in 55.9% (arm A) and 53.2% (arm B) of patients. Second-line therapy was administered for a median duration of 5.0 versus 3.2 months (P < .001) in study arm A versus B. Progression-free (6.5 v 4.7 months; hazard ratio, 0.68; 95% CI, 0.54 to 0.85; P < .001) and overall survival (16.3 v 13.2 months; hazard ratio, 0.70; 95% CI, 0.55 to 0.88; P = .0021) from start of second-line therapy were longer in patients in arm A compared with arm B. Conclusion: Our data suggest that the sequence of drug application might be more important than exposure to single agents. In patients with RAS wild-type tumors, first-line application of anti–epidermal growth factor receptor–directed therapy may represent a favorable condition for promoting effective subsequent therapy including antiangiogenic agents.
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“Cetuximab and panitumumab are monoclonal antibodies (mAbs) against epidermal growth factor receptor (EGFR) that are effective agents for metastatic colorectal cancer (mCRC).”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [4]
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Metadata
- Authors
- Modest, D. P., Stintzing, S., von Weikersthal, L. F., Decker, T., Kiani, A., Vehling-Kaiser, U., Al-Batran, S.-E., Heintges, T., Lerchenmüller, C., Kahl, C., Seipelt, G., Kullmann, F., Stauch, M., Scheithauer, W., Held, S., Möhler, M., Jung, A., Kirchner, T., & Heinemann, V.
- Affiliations
- German Cancer Research Center (DE)
- Dominik P. Modest, Sebastian Stintzing, and Volker Heinemann, University Hospital Grosshadern; Andreas Jung and Thomas Kirchner, University of Munich, Munich; Dominik P. Modest, Sebastian Stintzing, Volker Heinemann, Andreas Jung, and Thomas Kirchner, German Cancer Consortium and German Cancer Research Centre, Heidelberg; Ludwig Fischer von Weikersthal, Gesundheitszentrum St Marien, Amberg; Thomas Decker, Oncological Practice, Ravensburg; Alexander Kiani, Klinikum Bayreuth, Bayreuth; Ursula Vehling...
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2015-11-10
- Volume
- 33
- Issue
- 32
- Pages
- 3718-3726
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2110977364
- Cited by
- 121
- References
- 20
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 14 · 2022: 5 · 2021: 8 · 2020: 16 · 2019: 10 · 2018: 12 · 2017: 23 · 2016: 19 · 2015: 2
- FWCI
- 8.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Health Sciences › Medicine › Surgery › Intraperitoneal and Appendiceal Malignancies
- Keywords
- metastatic colorectal cancer, KRAS wild-type tumors, FIRE-3 trial, FOLFIRI, cetuximab, bevacizumab, panitumumab, second-line therapy, third-line therapy, anti-EGFR therapy, anti-angiogenic therapy, oxaliplatin, treatment sequencing, progression-free survival, overall survival
- MeSH terms
- Bevacizumab, Cetuximab, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Camptothecin, Leucovorin, Female, Fluorouracil, Humans, Male, Middle Aged, Proto-Oncogene Proteins, Colorectal Neoplasms, Proto-Oncogene Proteins p21(ras), Treatment Outcome, Disease-Free Survival, ras Proteins, Kaplan-Meier Estimate
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