Impact of skeletal muscle index (SMI) loss during palliative systemic treatment (Tx) on time to progression and overall survival (OS) in metastatic colorectal cancer (mCRC) patients.

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10087 Background: Evidence for a strong link between skeletal muscle depletion and poor outcomes in mCRC is growing. However, the impact of SMI changes over time on progression and OS during palliative systemic Tx is not known. The CAIRO3 study (Simkens et al. Lancet 2015) randomized 556 mCRC patients after 6 cycles capecitabine+oxaliplatin+bevacizumab (CAPOX-B) to maintenance CAP-B Tx (Main) vs. observation (Obs). Upon 1st disease progression (PD1), CAPOX-B or other treatment was reintroduced until 2nddisease progression (PD2). This is the first analysis using scan data of multiple time-points to investigate SMI changes during palliative systemic treatment Tx and its association with survival. Methods: 1227 CT-scans of a random selection of 416 CAIRO3 patients (mean age 64±9 years, Main n = 206; Obs n = 210) were analyzed for SMI (skeletal muscle area at the L3 level in cm2/m2). Using mixed model analysis, SMI changes were analyzed for two intervals; interval 1: from randomization to PD1, and interval 2: from PD1 to PD2. Three Cox regression models were used to study the association between SMI loss and time to PD2 and death for interval 1, and time to death for interval 2. Main and Obs groups were combined in the analyses since the p-value for interaction was not significant. Hazard ratios (HR) were reported per 2 units change in SMI. Results: Median times from randomization to PD1, PD2 and death were 7.7, 13.5 and 24 months resp. During interval 1 (less intensive or no Tx) patients gained SMI on average (1.2 units; 95%CI 0.6-1.8), but 23% of patients still lost SMI. SMI loss was associated with shorter time to PD2 (HR 0.88; 0.81-0.98, p= .01), but not with shorter OS (HR 0.94; 0.86-1.02, p= .17). During interval 2 (more intensive Tx) average SMI loss was -2.2 units ( 1.5-2.8) and 63% of patients lost SMI. SMI loss was associated with shorter OS (HR 0.73; 0.62-0.86, p< .00). Conclusions: Loss of SMI was related to shorter time to progression during first line less intensive main Tx or obs and shorter overall survival during more intensive reinduction Tx. This large longitudinal study suggests that SMI preservation may be a therapeutic goal. Clinical trial information: NCT00442637.