Koopman, Miriam

6 Background: Rates and survival outcomes for second-line therapy for mCRC for OA vs. YA are poorly understood. Methods: Pts with available subsequent treatment data after progression from 10 1st line trials were included. Associations between key clinical/disease characteristics, time to initial progression (TTiP) and rate of receipt of second-line therapy were evaluated. Time to progression (TTP) and overall survival (OS) were compared between OA and YA who were enrolled on second-line trials by Cox regression, adjusting for age, sex, ECOG PS, number of metastatic sites, presence of metastasis in lung/liver/peritoneum. Results: OA comprised 16.4% of first-line trials. OA and ECOG PS >0 were less likely to receive second-line therapy than YA. Odds of receiving second-line therapy decreased by 11% for each additional decade of life in multivariate analysis (p=0.0117). OA enrolled in second-line trials experience similar mTTP and mOS as YA (5.1 vs. 5.2mos; 11.6 vs 12.4mos, respectively). Conclusions: OA are less likely to receive 2nd line therapy for mCRC. We did not observe a statistical difference in survival outcomes for OA vs. YA following second-line therapy. Further study is needed to examine unmeasured factors, including comorbidity and functional status given observed inferior outcomes among adults with ECOG PS >0, and consideration given to inclusion of geriatric assessment to select OA likely to benefit from 2nd line therapy for mCRC. [Table: see text]

658 Background: In patients (pts) with mCRC with an asymptomatic primary tumor, there is limited evidence regarding the indication for primary tumor resection. The primary objective was to evaluate the prognostic value of primary tumor resection in synchronous mCRC pts. Methods: In this IPD analysis, a total of 3,423 pts from 8 first-line randomized trials (RCTs) with systemic therapy in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were analyzed. Five RCTs included targeted (anti-VEGF and/or anti-EGFR) agents. Synchronous mCRC was defined as distant metastases occurring ≤ 6 months of the initial CRC diagnosis. Overall survival (OS) and progression-free survival (PFS) were compared by stratified multivariate Cox models. Results: There were 710 (21%), 1,705 (50%) and 1,008 (29%) pts with non-resected and resected synchronous mCRC and metachronous mCRC, respectively. Compared to the non-resection group, pts in the synchronous resection group were associated with female gender, colon tumor, isolated liver/lung involvement, single metastatic site, and lower LDH (all p<.001). Adjusted for age, gender, performance status and prior chemotherapy, the non-resection group had a significantly worse median OS (16.4m) compared to the resection (22.2m; HR 1.60, 95% CI 1.43-1.78) and metachronous (22.4m; HR 1.81, 95% CI 1.58-2.07) groups. Similarly, PFS was significantly worse for the non-resection group (7.9m) compared to the resection (9.7m; HR 1.31, 95% CI 1.19-1.44) and metachronous group (8.9m; HR 1.47, 95% CI 1.30-1.66). Similar trends were observed in pts treated with non-targeted vs targeted agents, and anti-VEGF vs anti-EGFR therapy. In a subset analysis (n= 526), the observed associations remained after additional adjustment for primary tumor location, liver/lung involvement, number of metastatic sites, BMI and LDH. Conclusions: In this largest IPD analysis of mCRC trials to date, primary tumor resection is associated with better OS and PFS in synchronous mCRC pts. These results may be subject to bias since reasons for (non)resection were not available. Prospective RCTs on this topic are ongoing.