Abstract 2579: Loss of chromosome 18q11.2-18q12.1 is predictive for progression-free survival in metastatic colorectal cancer patients treated with bevacizumab
Authors: Dijk Erik van , Biesma Hedde , Cordes Martijn , Smeets Dominiek , Neerincx Maarten , Das Sudipto , Murphy Verena , Barat Anna , Bacon Orna , Prehn Jochen H.M. , Betge Johannes , Timo Gaiser , Fender Bozena , Meijer Gerrit A. , McNamara Deborah A. , Klinger Rut , Koopman Miriam , Ebert Matthias P.A. , Kay Elaina W. , Hennessey Bryan T. , Verheul Henk M.W. , Gallagher William M. , O'Connor Darran P. , Punt Cornelis J.A. , Loupakis Fotios , Lambrechts Diether , Byrne Annette , Grieken Nicole C.T. van , Ylstra Bauke 
Published: August 2018

Introduction: Most patients with metastatic colorectal cancer (mCRC) have a limited benefit from the addition of bevacizumab to standard combination chemotherapy. However, a subset of patients benefits substantially, highlighting an unmet clinical need for a predictive biomarker of response to bevacizumab. Previously, we demonstrated that losses in chromosome 5q34, 17q12 and 18q12.1-21.1 have a significant correlation with progression free survival (PFS) in patients treated with, but not without bevacizumab. These data warrant extensive validation. Patients: For validation, two cohorts of patients that received bevacizumab were analysed, one of 121 mCRC patient samples of the European multicenter study Angiopredict and one of 81 mCRC patient samples from the Italian multicenter study MoMA. A third cohort was included of 90 mCRC samples from patients that did not receive bevacizumab. Genome wide copy number aberrations were correlated with PFS, Results: Loss of chromosome 18q11.2-18q21.1 most significantly associated with PFS in both cohorts that received bevacizumab (Angiopredict: HR=0.61, p=0.016; MoMa: HR=0.55, p=0.019). No significant association with PFS was observed in the cohort that did not receive bevacizumab (HR=0.85, p=0.67). Patients of all three cohorts without an 18q11.2-21.1 loss had similar PFS regardless of treatment (Angiopredict, median PFS 211 days; MoMa, median PFS 232 days; no bevacizumab, median PFS 189 days). No significant associations with PFS were found for chromosome 5q34 and 17q for any of the cohorts. Conclusion: We conclude that loss of chromosomal region 18q11.2-18q21.1 is consistently predictive for PFS in patients receiving bevacizumab. 18q11.2 loss provides an increase in median PFS of 83 days, compared to patients without this loss. No significant increase was found for patients that did not received bevacizumab.

Citation Format: Erik van Dijk, Hedde Biesma, Martijn Cordes, Dominiek Smeets, Maarten Neerincx, Sudipto Das, Verena Murphy, Anna Barat, Orna Bacon, Jochen H.M. Prehn, Johannes Betge, Gaiser Timo, Bozena Fender, Gerrit A. Meijer, Deborah A. McNamara, Rut Klinger, Miriam Koopman, Matthias P.A. Ebert, Elaina W. Kay, Bryan T. Hennessey, Henk M.W. Verheul, William M. Gallagher, Darran P. O'Connor, Cornelis J.A. Punt, Fotios Loupakis, Diether Lambrechts, Annette Byrne, Nicole C.T. van Grieken, Bauke Ylstra. Loss of chromosome 18q11.2-18q12.1 is predictive for progression-free survival in metastatic colorectal cancer patients treated with bevacizumab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2579.