Tezcan, Haluk

396 Background: The 12-gene Oncotype DXColon Cancer Assay is clinically validated as a predictor of recurrence risk in stage II colon cancer patients following surgery. We previously reported that the 12-gene assay led to 45% change in physician treatment (Tx) recommendations in a prospective study in MMR-P stage IIA colon cancer patients. Here, from the same prospective study, we report the influence of the 12-gene assay on patient Tx decisions, physician confidence, concordance in Tx choice between physicians and patients, and patient decisional conflict. Methods: Consecutive patients with resected stage IIA colon cancer who were candidates for adjuvant chemotherapy were enrolled by 105 physicians from 17 sites. Patient's tumor specimens were assessed by the 12-gene assay (RT-PCR) and MMR (IHC). Prior to and after receiving these results, patients completed surveys including (1) their Tx decisions (observation (Obs) vs. 5FU-monotherapy (5FU) vs. 5FU + oxaliplatin (Oxal)) and (2) indicators of decisional conflict. Results: 190 of 221 patients enrolled were evaluable including 139 who were MMR-P. Pre-assay: 46% of patients chose Obs, 3% 5FU, 7% Oxal, 2% other and 41% were undecided. Post-assay: 75% chose Obs, 12% 5FU, 11% Oxal, 3% other (undecided was not a possible response). Post-assay 129 (96%) of 135 definitive Tx decisions (Obs, 5FU, or Oxal) were concordant between patients and physicians compared to 49 (66%) of 74 definitive decisions pre-assay. In the majority of cases, patients (85%) and physicians (69%) reported that the assay influenced their Tx decisions. Assay results increased physician confidence in Tx recommendations in 126 (84%) and provided additional clinically relevant information to physicians in 129 (86%) of cases. Patient decisional conflict was significantly lower after assay results (p<0.001). Conclusions: In this prospective study, quantitative recurrence risk information provided by the 12-gene assay influenced Tx decisions for a majority of patients and physicians, increased physician confidence, improved concordance in Tx choice between patients and physicians and decreased patient decisional conflict.

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.

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.