1735PTrajectory of skeletal muscle index (SMI) loss during palliative systemic treatment (Tx) predicts time to progression (TTP) in metastatic colorectal cancer (mCRC) patients

Background: In mCRC patients, SMI loss is suggested to be related with poor survival. Little is known on the trajectory of SMI and its relation with TTP. The CAIRO3 study (Simkens, Lancet 2015) randomized 557 mCRC patients after 6 cycles CAPOX-B to maintenance CAP-B vs. observation (obs). Upon 1st disease progression (PD1), CAPOX-B or other Tx was reintroduced until 2nd progression (PD2). Here we study if SMI trajectory predicts TTP in CAIRO3. Methods: 104 randomly selected CAIRO3 patients (mean age 65.4±8.3 years) were analyzed for SMI (skeletal muscle area at the L3 level in cm2/m2) using 9-weekly repeated CT scans (854 in total). Joint longitudinal-survival modeling, using mixed effects models for longitudinal SMI measures and Cox regression models for TTP analysis, was used to estimate hazard ratios (HR) for absolute SMI and SMI trajectory (per unit SMI loss per month) during two time periods: p1) from randomization to PD1 and p2) from PD1 to PD2. SMI trajectories were modeled throughout each time period and change was investigated at 9 and 4 weeks pre-PD. Results: During p1 (less intensive CAP-B / obs), patients gained SMI (mean +1.1 ±3.2 cm2/m2). Absolute SMI was not related with PD1 (HR SMI 9 weeks pre-PD1 0.99 [0.96-1.02], 4 weeks pre-PD1 0.99 [0.96-1.02]). A decrease in SMI preceding PD1 showed a higher, but non-significant, risk of early PD1 (HR SMI change 9 weeks pre-PD1 1.04 [0.83-2.56], 4 weeks pre-PD1 1.53 [0.91-2.55]. During p2, (more intensive CAPOX-B / other Tx), patients lost SMI (mean -2.7 ±3.4 cm2/m2). Both SMI and SMI trajectory were significantly related to PD2 (HR SMI 9 weeks pre-PD2 1.03 [1.01-1.08], 4 weeks pre-PD2 1.04 [1.01-1.08], SMI change 9 weeks pre-PD2 1.37 [1.07-1.75], 4 weeks pre-PD2 1.23 [0.83-1.82]). Conclusions: In mCRC patients, a decrease in SMI tended to predict shorter TTP during less intensive CAP-B or obs. SMI and SMI trajectory predicted shorter TTP during more intensive CAPOX-B or other reintroduction Tx. This large longitudinal analysis is the first to show that the trajectory of SMI loss predicts early TTP. These data suggest that SMI preservation may be a therapeutic goal. Clinical trial identification: NCT00442637. Legal entity responsible for the study: Anne May. Funding: Province of Utrecht, The Netherlands and the Dutch Colorectal Cancer Group (DCCG). Disclosure: B.D. Dorresteijn, M. Jourdan: Employee: Nutricia Research. All other authors have declared no conflicts of interest.