Meeting
2020 ASCO Virtual Scientific Program
High amphiregulin mRNA expression is a strong prognostic biomarker with response to cetuximab in FIRE-1, CIOX, and FIRE-3.
Authors
Arndt Stahler
Department of Medicine III, University Hospital, LMU Munich, Munich, Germany
Arndt Stahler , Sebastian Stintzing , Dominik Paul Modest , Ingrid Ricard , Christine Kapaun , Boryana Ivanova , Ursula Vehling-Kaiser , Ludwig Fischer von Weikersthal , Andreas Schalhorn , Martina Stauch , Alexander Kiani , Jens Neumann , Thomas Kirchner , Volker Heinemann
Organizations
Department of Medicine III, University Hospital, LMU Munich, Munich, Germany, Medical Department, Division of Hematology, Oncology, and Tumor Immunology (CCM), Charité Universitätsmedizin Berlin, Berlin, Germany, Comprehensive Cancer Center, University Hospital, LMU Munich, Munich, Germany, MVZ St. Cosmas, Neubiberg, Germany, Institute of Pathology, Munich, Germany, Practice for Medical Oncology, Landshut, Germany, MVZ Amberg, Amberg, Germany, Department of Medical Oncology, Klinikum Grosshadern, University of Munich, Munich, Germany, Onkologische Schwerpunktpraxis Kronach, Kronach, Germany, Klinikum, Bayreuth, Germany, Department of Pathology, University of Munich, Munich, Germany, University Hospital Munich, LMU Munich, Munich, Germany
Research Funding
No funding received
None
Background: Amphiregulin (AREG) and epiregulin (EREG) were discussed as biomarkers for treatment of metastatic colorectal cancer (mCRC). Data from randomized controlled trials (RCT) are limited. Methods:AREG and EREG mRNA expression by RTqPCR in relation to housekeeping genes were available from 688 patients of three RCT (FIRE-1, n = 192, FUFIRI vs. mIrOx; CIOX, n = 113, cetuximab + CAPIRI/CAPOX; FIRE-3, n = 383, FOLFIRI+cetuximab/bevacizumab) and were normalized to their respective range of each trial with median and 3rd quartile as threshold values. Kaplan-Meier estimated overall survival (OS) and progression-free survival (PFS). Cox regression analysis calculated hazard ratio (HR) and 95% confidence interval (95% CI). Overall response rate (ORR) was compared by chi square test. Results: Across all trials, high AREG mRNA expression appeared as strong prognostic biomarker for OS, PFS and ORR for all threshold values. In RAS wildtype patients, high AREG expression was associated with better OS and PFS for cetuximab but not bevacizumab treatment. (Table) No effects were seen for epiregulin when all trials were analysed together. Conclusions: High AREG mRNA expression appeared as strong prognostic biomarker in mCRC. Positive predictive information might exist for cetuximab treatment.
| < median | > median | < 3rd quartile | > 3rd quartile | |
|---|---|---|---|---|
| All patients | ||||
| n FIRE-1 | 103 | 89 | 152 | 42 |
| n CIOX | 60 | 53 | 86 | 27 |
| n FIRE-3 | 181 | 202 | 279 | 104 |
| OS, months | 21.5 | 26.2 | 22.6 | 28.6 |
| HR [95% CI], p | 0.80 [0.68 – 0.94] p = 0.007 | 0.76 [0.63 – 0.92] p = 0.005 | ||
| PFS, months | 8.1 | 10.0 | 8.9 | 10.6 |
| HR [95% CI], p | 0.74 [0.63 – 0.86] p = 0.001 | 0.79 [0.68 – 0.94] p = 0.009 | ||
| ORR, % | 51.6 | 63.1 | 52.6 | 71.5 |
| P (Chi sq.) | 0.004 | < 0.0001 | ||
| RAS WT & bevacizumab treated patients | ||||
| n FIRE-3 | 66 | 68 | 99 | 35 |
| OS, months | 23.8 | 27.5 | 23.8 | 28.6 |
| HR [95% CI], p | 0.93 [0.65 – 1.33] p = 0.71 | 0.96 [0.65 – 1.43] p = 0.85 | ||
| PFS, months | 10.3 | 11.3 | 10.7 | 11.5 |
| HR [95% CI], p | 0.92 [0.65 – 1.30] p = 0.63 | 1.03 [0.70 – 1.53] p = 0.87 | ||
| RAS WT & cetuximab treated patients | ||||
| n CIOX | 34 | 32 | 47 | 19 |
| n FIRE-3 | 51 | 70 | 76 | 45 |
| OS, months | 23.5 | 36.6 | 24.5 | 37.1 |
| HR [95% CI], p | 0.60 [0.43 – 0.63] p = 0.002 | 0.61 [0.43 – 0.87] p = 0.006 | ||
| PFS, months | 7.8 | 10.6 | 8.6 | 11.2 |
| HR [95% CI], p | 0.66 [0.49 – 0.88] p = 0.006 | 0.77 [0.56 – 1.05] p = 0.10 | ||
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Abstract Details
Session Type
Poster Session
Session Title
Gastrointestinal Cancer—Colorectal and Anal
Track
Gastrointestinal Cancer—Colorectal and Anal
Sub Track
Colorectal Cancer–Advanced Disease
Citation
J Clin Oncol 38: 2020 (suppl; abstr 4026)
DOI
10.1200/JCO.2020.38.15_suppl.4026
Abstract #
4026
Poster Bd #
18
Abstract Disclosures
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