Abstract 481P
Background
Bevacizumab-based chemotherapy is the recommended first-line therapeutic strategy for metastatic colorectal cancer (mCRC). Yet, some patients do not benefit from this association and until now robust predictive or prognostic biomarker with clinical practice applicability have not been identified. Serum analysis by mid-infrared spectroscopy (SMIRS) allows a rapid and non-invasive metabolomic profiling of an individual. Its prognostic value has never been assessed in mCRC. The aim of this study was to evaluate the prognostic yield of SMIRS in patients receiving first-line bevacizumab-based treatment for mCRC.
Methods
We conducted an ancillary analysis from a multicentre prospective study (NCT00489697). All baseline serums were screened by attenuated total reflection method. Principal component analysis and unsupervised k-mean partitioning methods were performed blinded to all patients’ data. Endpoints were progression-free survival (PFS) and overall survival (OS).
Results
From the 108 included patients, two prognostic groups defined by spectral signatures were blindly discriminated by SMIRS. First group patients (n = 25) had lower body mass index (p = 0.026) and albumin levels (p < 0.001). They had higher levels of angiopoietin-2, vascular endothelial growth factor, lactate dehydrogenase and carcinoembryonic antigen (p < 0.001 for all). Their spectral signature differed according to six significative absorption bands corresponding to lipid deficiency and different sugar and protein composition. They had less grade 1-2 bevacizumab-related toxicity (p = 0.041). Their best objective response rate was worse: 52.0% vs 73.5% (p = 0.043). In univariate analysis, their OS and PFS were shorter with respective medians: 17.6 vs 27.9 months (p = 0.02) and 8.7 vs 11.3 months (p = 0.03). In multivariate analysis, PFS was significantly shorter (HR: 1.74, 95% CI [1.07-2.82], p = 0.025) with a similar trend for OS (HR: 1.69, 95% CI [0.98-2.93], p = 0.061).
Conclusions
By metabolomic fingerprinting, SMIRS on baseline serum proves to be a promising prognostic tool for patients receiving first-line bevacizumab-based chemotherapy for mCRC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Thierry Lecomte.
Funding
INCa (Institut National du Cancer), CGO (Cancéropôle Grand-Ouest), SNFGE (French National Society of Gastroenterology), French Higher Education and Research Ministry.
Disclosure
O. Bouche: Financial Interests, Personal, Invited Speaker: Merck KGaA; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Astra-Zeneca; Financial Interests, Personal, Invited Speaker: Grunenthal; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Invited Speaker: Pierre Fabre. All other authors have declared no conflicts of interest.