Evolution of skeletal muscle mass (SMM) during palliative systemic treatment in metastatic colorectal cancer (mCRC) patients participating in the randomized phase 3 CAIRO3 study

Observational studies suggest that low SMM is associated with chemotherapy-related toxicity and poor survival in mCRC patients. Little is known about patterns of SMM during palliative systemic therapy. Here we use data of the CAIRO3 study (Simkens et al. Lancet 2015) in which mCRC patients with stable disease or better after 6 cycles capecitabine + oxaliplatin + bevacizumab (CAPOX-B) were randomized between maintenance treatment with capecitabine + bevacizumab (CAP-B, M) and observation (O). In both groups CAPOX-B or other treatment was reintroduced upon disease progression until second disease progression, which was also the primary study endpoint. We used repeated scan data of 101 CAIRO3 patients to investigate SMM during treatment. 307 CT-scans of 101 randomly chosen CAIRO3 patients (63.1 ± 9.0 years, M n = 51; O n = 50) were analyzed for SMM at four time points (i.e. prior to start pre-randomization induction treatment, at randomization, at first and at second disease progression) using single slice evaluation at L3. A linear mixed effects model was used to assess SMM changes both within and between study arms. Before CAIRO3 randomization during 6 cycles of CAPOX-B induction treatment, SMM decreased significantly in all patients (M: -0.8kg, (95% CI -0,14; -1,2) and O: -0,7kg (-0,4; -1,6)). After randomization, SMM recovered during maintenance treatment by 0,2kg (-0.3; 0,8) and observation -0.5kg (-1,1; 0,2) both compared to pre-induction SMM levels (median time 9.0 months and 4.3 months for M and O, respectively). After first progression and during reinduction treatment with CAPOX-B or other treatment, SMM again decreased significantly and similarly in both arms, M: -0,9kg (-0,1; -1.6), and O: -1,5kg (-0,8; -2,3) compared to pre-induction SMM levels (median time from first progression until second progression M: 4,7 months and O: 6,1 months). Our data shows that muscle loss in mCRC patients during palliative systemic therapy is reversible and varies with treatment regimen. Although studies have shown prognostic capacity for SMM, the effect of subsequent changes in SMM are unknown and may be clues for new future therapeutic interventions.