Bevacizumab combined with 1st line chemotherapy in elderly patients with metastatic colorectal cancer: Are there good prognostic indicators?
Authors: C. Borges, J. Simões, C. Lemos, C. Fernandes, C. Sarmento, M. Damasceno, D. Almeida
Journal: Annals of Oncology (2018)

Introduction: As population ages, the incidence of metastatic colorectal cancer (mCRC) amongst elderly patients (>65 years old) rises. However, the geriatric population is a heterogeneous subset of patients, ranging from very fit to very frail, and often underrepresented in clinical trials. Studies suggest that elderly patients may benefit from target therapies as their younger counterparts, but careful clinical and analytical geriatric assessment is necessary in order to individualize treatment approach. The aim of our study is to evaluate the prognostic value of tumor markers and markers of systemic inflammation, in senior patients with mCRC, treated with anti-VEGF in 1st line palliative systemic treatment. Methods: Retrospective analysis of 52 patients, over 65 years old, treated with bevacizumab in 1st line palliative chemotherapy between 2008 and 2017. Pretreatment CEA and CA 19.9 concentrations were ascertained, as well as the following inflammation markers: modified Glasgow prognostic score (mGPS), neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR) and platelet/lymphocyte ratio (PLR). Progression free survival (PFS) and overall survival (OS) analysis was calculated using Kaplan-Meier method and Cox hazard regression, with a significance level of 0,05. Results: Our population's median age was 69 years (CI 95% 65-76). Mean PFS was 16 months, 10 months and 19 months, for patients aged < 70 years, 70 to 75 years and over 75 respectively. Mean OS was 26 months, 18 months and 36 months, for patients aged < 70 years, 70 to 75 years and over 75 respectively. The patient age was not significantly associated with either PFS or OS. There was no significant survival difference between right and left side (p = 0,569 for PFS; p = 0,330 for OS) and between KRAS wt/mut (p = 0,986 for PFS; p = 0,140 for OS). Over 50% had liver metastasis and 37% underwent liver metastasectomy. Concomitant chemotherapy protocol was irinotecan-based in 63,5%, oxaliplatin-based in 30,8% and capecitabine monotherapy in 5,8% of patients. Mean CEA value was 11,75 ng/mL (CI95% 1,79-3457,85) and CA 19.9 was 32 U/mL (CI95% 0-6259). Patients with elevated CEA concentrations had a significantly worse PFS than regular concentrations (median 10.8 vs 18.7 months, p = 0.047), but not OS. Multivariate analysis confirmed the findings for PFS (HR 1,39, CI95% 0,59-3,26, p = 0,030). Four percent had elevated mGPS, 50% elevated NLR, 34,6% reduced LMR and 53,8% elevated PLR. OS and PFS analysis failed to demonstrate a prognostic role for inflammatory markers. However, multivariate analysis suggested that the presence of three or more inflammatory criteria was associated with a trend towards worse OS (HR 0,45, CI95% 0,20-1,05, p = 0.066) and worse PFS (HR 0,79, CI95%, 0,38-1,29, p = 0,098). Conclusion: We concluded that CEA concentration may be a valuable negative prognostic marker for PFS, in elderly patients treated with bevacizumab. Concomitant presence of elevated mGPS, elevated NLR, reduced LMR and/or elevated PLR was associated with a trend towards worse outcomes. However, further prospective studies might lead to better risk stratification.