Fish, Susan

514 Background: Randomized trials and OCSs have demonstrated that BV treatment in 1st-line (1L), in 2L, and across multiple lines is associated with longer survival in patients (pts) with mCRC. This analysis was aimed at comparing the effectiveness of BV after 1st disease progression (PD) between male and female mCRC pts who received 1L BV-containing therapy in a real-world setting. Methods: ARIES is a large, prospective OCS that enrolled pts who received BV and chemotherapy (CT) for 1L mCRC. Post-PD effectiveness was assessed for men and women characterizing BV use by cumulative and dichotomous approaches. The primary analysis treated BV exposure as cumulative BV doses after 1st PD and post-progression overall survival (ppOS) as the time from 1st PD to death. A time-dependent Cox regression model was fitted to assess the effect of cumulative BV exposure on ppOS, while controlling for potential confounders. A dichotomous secondary analysis characterized BV exposure as receipt of CT + BV (BBP) or CT alone (No BBP) within 2 months after PD and ppOS as time from 1st PD + 2 months to death. Results: Among the 1,550 1L mCRC pts enrolled, 1,199 (532 women) had PD. In the primary analysis, hazard ratios (HRs) for ppOS decreased, on average, by 1.2% with each additional BV dose. When stratified by sex, the average risk reduction per BV dose over 15 doses was 1.8% in women and 0.7% in men. In the secondary analysis that included 331 women (BBP, 180; No BBP, 151) and 417 men (BBP, 245, No BBP, 172) who received BV ± CT within 2 months post-PD, the HRs for ppOS with BBP treatment were 0.46 (95% CI, 0.35–0.59) in women and 0.52 (95% CI, 0.41–0.67) in men. Statistical interaction tests for differences in the effectiveness of BV between men and women were negative for primary and secondary analyses (P of 0.58 and 0.77). Protocol-specified adverse events occurred in 17.8% of women and 10.2% of men in the BBP population; this difference was largely related to rates of hypertension (8.3% vs 2.4%, respectively). Conclusions: In ARIES, the effectiveness of BV after first PD was not statistically different between women and men with mCRC. Clinical trial information: NCT00388206.

702 Background: Median overall survival (OS) in mCRC has significantly improved over the past 20 yrs, but the observed range of OS in pts remains wide; a large percentage of pts have OS <1 yr or >4 yrs. ARIES was a prospective OCS conducted from 2006–2012 that evaluated outcomes in pts receiving BV + chemotherapy (CT) for mCRC in general clinical practice. The objective of this analysis is to examine clinical characteristics of pts with long vs short OS. Methods: This analysis included 1,417/1,550 first-line (1L) BV-treated mCRC pts who died or had complete follow-up on study. Long OS was defined as OS within the upper quartile of the analysis population (range 42–67 mos); short OS was defined as OS within the lower quartile (range 0.3–12 mos). Progression-free survival (PFS) was estimated using Kaplan-Meier methods. Pt and disease characteristics and treatment patterns were described using summary statistics. Results: Pt and disease characteristics are shown in the Table. Median PFS was 22.3 mos (95% CI, 19.9–23.3) vs. 4.9 mos (95% CI, 4.6–5.4), in the long-OS vs. short-OS groups. More pts with long OS received any second-line (2L) therapy (71% vs. 46%), and were exposed to 5-fluorouracil, oxaliplatin, and irinotecan throughout the course of their disease (53% vs. 32%) compared with pts with short OS. KRAS/BRAF mutation status was not collected. Conclusions: Pts with long OS had better baseline performance status, primary tumors more likely to have been resected, and were more likely to have received 2L CT. Additional analyses of detailed treatment patterns and safety are ongoing. Clinical trial information: NCT00388206. [Table: see text]

535 Background: Prior ARIES analyses showed that BV-treated mCRC patients (pts) receiving chemotherapy (CT)/biologics + BV within 2 months (mo) after 1st progressive disease (PD) had longer post-progression survival (PPS) than pts receiving only CT/biologics. The present analysis evaluated whether this effect of BV was consistent when used with common 2L CT regimens— irinotecan- (iri-) and oxaliplatin- (ox-) based—in mCRC pts exposed to 1L BV in ARIES. Methods: ARIES enrolled mCRC pts receiving 1L CT + BV. No tx regimens or assessments were protocol specified. This analysis evaluated 1L BV-treated mCRC pts who had PD, survived ≥2 mo after PD, and received 2L iri- or ox-based tx. PPS was estimated by Kaplan-Meier methods. Cox regression was used to estimate hazard ratios (HRs), while adjusting for covariates (eg, 1L time to progression). Results: Of 1550 1L pts in ARIES, 1074 had 1st PD and survived ≥2 mo after PD. Of these 1074, 390 and 114 received 2L iri- and ox-based tx, respectively, ± BV ( table ). Baseline characteristics were generally similar between groups. The incidence of targeted adverse events (TAEs) was as expected and similar between the BV and No BV groups over time. In pts receiving 2L iri- or ox-based CT tx, PPS in BV-treated pts was longer compared to those not on BV. Analyses may be limited by small pt numbers in some groups. Conclusions: Consistent with prior ARIES analyses, the continued use of BV after 1st PD was associated with prolonged PPS regardless of the 2L CT backbone used. [Table: see text]

ABSTRACTPurposeThis analysis from Avastin® Registries: Investigation of Effectiveness and Safety (ARIES) examined the association between exposure to bevacizumab after disease progression (PD) and postprogression survival (PPS) in bevacizumab‐exposed metastatic colorectal cancer (mCRC) through the application of time‐dependent and time‐fixed analytical methods.MethodsPatients with mCRC who were treated with first‐line bevacizumab and who survived first PD (PD1) were included. A time‐dependent Cox regression model was fitted to assess the effect of cumulative bevacizumab exposure on PPS, while controlling for potential confounders. In addition to support findings from previous studies, a modified intent‐to‐treat (mITT) analysis compared PPS in patients who received bevacizumab beyond disease progression (BBP) with those who did not (No‐BBP).ResultsOf 1550 patients, 1199 survived PD1 and had a median PPS of 13.4 months. Cumulative bevacizumab exposure was associated with improved PPS (p = 0.0040). After adjusting for confounders, the hazard ratios (HRs) for PPS decreased, on average, by 1.2% (range, 1.1–1.3%) with each additional dose of bevacizumab. In the mITT analysis, the median PPS for BBP (n = 438) was 14.4 months vs 10.6 months with for No‐BBP (n = 667). BBP was found to be independently associated with longer PPS in a multivariable Cox regression analysis (HR, 0.84; 95% confidence interval, 0.73–0.97). Protocol‐specified adverse events suspected to be associated with bevacizumab occurred in 13.0% of patients with BBP.ConclusionThis analysis supports the observation that bevacizumab exposure after PD1 is associated with longer PPS in mCRC. Copyright © 2014 John Wiley & Sons, Ltd.

Abstract Background. The Avastin® Registry: Investigation of Effectiveness and Safety (ARIES) study is a prospective, community-based observational cohort study that evaluated the effectiveness and safety of first-line treatment patterns, assessing the impact of chemotherapy choice and treatment duration. Methods. The ARIES study enrolled patients with metastatic colorectal cancer (mCRC) receiving first-line chemotherapy with bevacizumab and followed them longitudinally. The protocol did not specify treatment regimens or assessments. Analyses included all patients who initiated bevacizumab in combination with either first-line oxaliplatin with infusional 5-fluorouracil and leucovorin (FOLFOX) or irinotecan with infusional 5-fluorouracil and leucovorin (FOLFIRI). Progression-free survival (PFS) and overall survival (OS) times were estimated using Kaplan–Meier methods. Hazard ratios (HRs) were estimated with multivariate Cox regression analysis, adjusting for potential confounding factors. Results. In total, 1,550 patients with first-line mCRC were enrolled (median follow-up, 21 months) and most received FOLFOX–bevacizumab (n = 968) or FOLFIRI–bevacizumab (n = 243) as first-line therapy. The baseline characteristics and median treatment duration were generally similar between subgroups. There were no significant differences in the median PFS (10.3 months vs. 10.2 months) or OS (23.7 months vs. 25.5 months) time between the FOLFOX–bevacizumab and FOLFIRI–bevacizumab subgroups, respectively, by unadjusted analyses. Multivariate analyses showed FOLFIRI–bevacizumab resulted in a similar PFS (HR, 1.03; 95% confidence interval [CI], 0.88–1.21) and OS (HR, 0.95; 95% CI, 0.78–1.16) outcome as with FOLFOX–bevacizumab. The incidence proportions of bevacizumab-associated adverse events were similar for FOLFOX- and FOLFIRI-based therapies. Conclusions. In first-line mCRC patients, the FOLFOX–bevacizumab and FOLFIRI–bevacizumab regimens were associated with similar treatment patterns and clinical outcomes.