Baseline absolute neutrophil counts (ANC) and survival in second-line metastatic colorectal cancer (mCRC) patients (pts).

Abstract

713 Background: Exploratory analyses from RAISE (NCT01183780), FOLFIRI with ramucirumab or placebo in previously treated mCRC pts, suggested pts with treatment-emergent neutropenia may have improved overall survival (OS) compared to pts who did not experience neutropenia on study (Ciuleanu T, et al. abst. 2475, ESMO 2016). Subsequent analyses suggested an even stronger association between baseline ANC and OS, with high baseline ANC associated with shorter OS. A retrospective observational study was conducted to test this association as a pre-specified hypothesis. Methods: The IMS Oncology Database (electronic medical record data from US community practices) was used to identify pts ≥ 18 yrs with mCRC (ICD-9 code 153.x, 154.0 or 154.1) who initiated second-line fluoropyrimidine and irinotecan (+/- bevacizumab; bev) in 2007-2013, following progression during or after first-line fluoropyrimidine and oxaliplatin (+/- biologic). Eligible pts had ≥ 1 ANC in the 60 days prior to second-line therapy. Pts were stratified by second-line bev use and high/low baseline ANC ( ≥ or < 5.5x109/L) and matched by propensity scores. OS based on a validated proxy was analyzed using the Kaplan-Meier method and a Cox proportional hazards model, adjusted for age, gender, ECOG PS, stage, length of first-line treatment, and BMI. Results: 747 eligible pts were identified, of whom 617 were matched. Pts with baseline characteristic data had a median age of 59 yr, 57% were male, 67% were Caucasian, 74% had stage IV disease at diagnosis, and 63% had ECOG PS of 0/1 at start of second-line. Bev-treated pts with high baseline ANC (n = 122) had a median OS (mOS) of 7.7 mo vs 14.7 mo in pts with low baseline ANC (n = 323); adjusted HR 1.69 (95% CI, 1.35, 2.12; p < 0.0001). Pts with high baseline ANC not treated with bev (n = 59) had a mOS 5.4 mo vs 14.4 mo in pts with low baseline ANC (n = 113); adjusted HR 2.73 (95% CI, 1.89, 3.93; p < 0.0001). There was a modest interaction effect between bev treatment and baseline ANC (p = 0.012), indicating greater bev benefit in the high ANC group. Conclusions: Baseline ANC appears to be a strong prognostic factor and potentially a weak predictive factor for antiangiogenic therapy for OS in pts with previously treated mCRC.