Meeting
2015 Gastrointestinal Cancers Symposium
Influence of adjuvant pretreatment on outcome of FIRE-3 (AIO KRK-0306): A randomized phase III study of FOLFIRI plus cetuximab or bevacizumab as first-line treatment for wild-type (WT) KRAS (exon 2) metastatic colorectal cancer (mCRC) patients.
Authors
Sebastian Stintzing
Department of Hematology and Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, LMU Munich, Munich, Germany
Sebastian Stintzing , Dominik Paul Modest , Ludwig Fischer von Weikersthal , 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 , Swantje Held , Clemens Albrecht Giessen , Markus Hermann Moehler , Andreas Jung , Thomas Kirchner , Volker Heinemann
Organizations
Department of Hematology and Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, LMU Munich, Munich, Germany, Department of Medical Oncology, Klinikum Grosshadern, University of Munich, Munich, Germany, Department of Oncology, Gesundheitszentrum St. Marien GmbH, Amberg, Germany, Onkologie Ravensburg, Ravensburg, Germany, Klinikum Bayreuth, Bayreuth, Germany, Practice for Medical Oncology, Landshut, Germany, Institute of Clinical Cancer Research at Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt am Main, Germany, Städtisches Klinikum Neuss Lukaskrankenhaus GmbH, Medical Department II, Neuss, Germany, Private Practice for Oncology, Muenster, Germany, Department for Hematology, Klinikum Magdeburg, Magdeburg, Germany, Onkologische Schwerpunktpraxis, Bad Soden, Germany, Klinikum Weiden, Weiden, Germany, Onkologische Schwerpunktpraxis Kronach, Kronach, Germany, Medical University of Vienna, Vienna, Austria, ClinAssess GmbH, Leverkusen, Germany, Department of Internal Medicine III, Klinikum Grosshadern, University of Munich, Munich, Germany, Johannes-Gutenberg University Mainz, Mainz, Germany, Department of Pathology, University of Munich, Munich, Germany
Research Funding
Other
Background: The FIRE-3 study (AIO KRK-0306) was designed to compare the efficacy of FOLFIRI + cetuximab (cet) to FOLFIRI + bevacizumab (bev) as first-line treatment in KRAS WT mCRC patients. FOLFIRI plus cet resulted in comparable overall response rates (ORR) and progression free survival (PFS) when compared to FOLFIRI + bev. Overall survival (OS) was significantly longer in the FOLFIRI + cet arm. Methods: In an exploratory subgroup analysis, patients pretreated with adjuvant chemotherapy were analyzed by Fisher's exact and log rank-test according to tumor response (ORR) and survival data. Patients of the ITT (n=592) and the final RAS wild-type population (n=400) were investigated. Results: See table. Conclusions: Results in patients treated with any adjuvant chemotherapy mirrored those in the whole study population. In adjuvant pretreated RASwt patients a significantly higher ORR was reached in the cet arm when compared to the bev arm (p=0.01). The role of adjuvant treatment on efficacy of first-line therapy remains to be further evaluated. Clinical trial information: NCT00433927
| Patients with any adjuvant chemotherapy (n=124) | ||||
|---|---|---|---|---|
| KRAS exon 2 wt | FOLFIRI + Cet N=68 | FOLFIRI + Bev N= 56 | P* | HR |
| ORR (%) | 60.3 | 48.2 | 0.21 | |
| PFS (95% CI) | 9.4 (7.4 – 12.3) | 9.7 (8.8 – 10.8) | 0.36 | 1.19 |
| OS (95% CI) | 33.1 (23.7 – 49.8) | 25.6 (19.4 – 42.9) | 0.26 | 0.77 |
| Patients pretreated with oxaliplatin (n=58) | ||||
| KRAS exon 2 wt | FOLFIRI + Cet N= 34 | FOLFIRI + Bev N= 24 | P* | HR |
| ORR (%) | 58.8 | 50.0 | 0.36 | |
| PFS (months) (95% CI) | 10.2 (6.8 – 12.8) | 10.3 (8.8 – 12.0) | 0.30 | 1.34 |
| OS (months) (95% CI) | 33.1 (23.7 – 38.5) | 44.3 (23.7 – 49.9) | 0.58 | 1.22 |
| Patients with any adjuvant chemotherapy (n=75) | ||||
|---|---|---|---|---|
| RASwt | FOLFIRI + Cet N=37 | FOLFIRI + Bev N= 38 | P* | HR |
| ORR (%) | 73.0 | 42.1 | 0.01 | |
| PFS (months) (95% CI) | 10.2 (6.8 – 12.3) | 9.6 (8.6 – 10.7) | 0.84 | 1.05 |
| OS (months) (95% CI) | 38.3 (25.2 – 52.0) | 25.6 (19.4 – 35.0) | 0.22 | 0.70 |
| Patients pretreated with oxaliplatin (n=36) | ||||
| RASwt | FOLFIRI + Cet N= 19 | FOLFIRI + Bev N= 17 | P* | HR |
| ORR (%) | 73.7 | 47.1 | 0.17 | |
| PFS (months) (95% CI) | 10.2 (7.2 – 13.3) | 9.9 (8.6 – 11.9) | 0.59 | 1.2 |
| OS (months) (95% CI) | 27.9 (18.3 – 52.0) | 44.3 (23.7 – 58.7) | 0.42 | 1.44 |
*p= log rank test p for OS and PFS, 2-sided Fisher’s exact test for ORR.
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 Details
Session Type
Poster Session
Session Title
General Poster Session C: Cancers of the Colon, Rectum, and Anus
Track
Cancers of the Colon, Rectum, and Anus
Sub Track
Prevention, Diagnosis, and Screening
Clinical Trial Registration Number
NCT00433927
Citation
J Clin Oncol 33, 2015 (suppl 3; abstr 515)
DOI
10.1200/jco.2015.33.3_suppl.515
Abstract #
515
Poster Bd #
A9
Abstract Disclosures
Similar Abstracts
Abstract
2023 ASCO Annual Meeting
Prognostic role of TP53 variants in the phase III study of FOLFIRI/cetuximab versus FOLFIRI/cetuximab followed by cetuximab (Cet) alone in first-line therapy of RAS and BRAF wild-type (wt) metastatic colorectal cancer (mCRC) patients (ERMES study).
First Author: Nicola Normanno
Abstract
2024 ASCO Gastrointestinal Cancers Symposium
Refining first-line treatment decision in RAS wildtype (RAS‑WT) metastatic colorectal cancer (mCRC) by combining clinical biomarkers: Results of the randomized phase 3 trial FIRE-3 (AIO KRK0306).
First Author: Julian Walter Holch
Abstract
2023 ASCO Gastrointestinal Cancers Symposium
Phase III FIRE-4 study (AIO KRK-0114): Evaluation of first-line treatment efficacy of FOLFIRI/cetuximab in patients with RAS-WT mCRC receiving the first cycle of treatment with chemotherapy only.
First Author: Sebastian Stintzing
Abstract
2023 ASCO Annual Meeting
Phase III FIRE-4 study (AIO KRK-0114): Influence of baseline liquid biopsy results in first-line treatment efficacy of FOLFIRI/cetuximab in patients with tissue RAS-WT mCRC.
First Author: Sebastian Stintzing