Impact of sarcopenia on dose limiting toxicities in metastatic colorectal cancer patients (mCRC pts) receiving palliative systemic treatment

Abstract

Background: Evidence is increasing that severe skeletal muscle (SM) loss (sarcopenia) is associated with reduced overall survival (OS) in mCRC pts. We recently found, using data of the randomized phase 3 CAIRO3 study (Lancet, 2015), that SM loss was related to shorter time to progression during first line maintenance treatment (Tx) with capecitabine+bevacizumab (CAP-B) or observation. Subsequently, SM loss during more intensive reinduction Tx by adding oxaliplatin (CAPOX-B) was associated to shorter overall survival (ASCO, 2017). As a potential risk factor for reduced survival we explored whether sarcopenia was associated with dose reductions at start of CAPOX-B reinduction Tx and dose limiting toxicities (DLT) during CAPOX-B reinduction Tx. Methods: Here, CAIRO3 pts were included who received CAPOX-B reinduction Tx. DLT were defined as any dose delay, reduction, or discontinuation of systemic treatment because of reported CTCAE (v3.0) toxicities at start or during Tx. Poisson regression models adjusted for relevant confounders were used to study the association between sarcopenia and DLT. Results: A total of 254 pts received CAPOX-B reinduction Tx. 39% of pts were sarcopenic and compared to normal SM pts we found no statistically significant differences in age and sex (sarcopenic vs normal SM: mean age 63.6±9.1 vs 61.9±8.5 yrs, p=.20 and 39% vs 31% females p=.31). BMI was significantly lower in sarcopenic pts, but pts were on average still overweight (25.9±3.8 vs 27.2±3.8 p=.01). Overall, 67% experienced ≥1 DLT. At start of CAPOX-B, 25% had already received a dose reduction and the risk of dose reduction at start was significantly higher for sarcopenic compared to normal SM pts (RR 1.8 95%CI 1.08-2.90). Despite more frequent dose reductions at start, sarcopenic pts did not have a significantly lower risk of DLT during CAPOX-B Tx (RR sarcopenic vs normal SM pts 0.86 95% CI 0.46-1.45). Conclusions: Sarcopenia was significantly associated with dose reductions at start of CAPOX-B reinduction Tx, and not with DLT during CAPOX-B reinduction Tx. Possible explanations for dose reductions at start might be more frequent toxicities during previous Tx including neuropathy.