Muscle quantity, quality and dynamics in metastatic colorectal cancer patients during third-line therapy with regorafenib or TAS102

Introduction: Regorafenib and TAS-102 showed similar efficacy as third- or subsequent-line treatment in Metastatic ColoRectal cancer (mCRC) patients. The aim of our study was to analyze the occurrence of sarcopenia and Skeletal Muscle Loss (SML) in mCRC patients during Regorafenib or TAS102 treatment. Materials and methods: Our retrospective analysis included 22 mCRC patients in third-line therapy with Regorafenib or TAS-102. Muscle tissue was evaluated at L3 level by CT scans and sarcopenia was assessed using Skeletal Mass Index [SMI=muscle area at L3 in cm2/(height in m)2]. Results: Mean±SD age was 67.7±9.8. 12/22 patients received Regorafenib, and 10/22 TAS102. 9/22(40.9%; 6M, 3F) patients were sarcopenic and 6/20 (30%; 2M, 4F) patients had low Muscle Attenuation (MA) at baseline CT. Sarcopenic patients had lower BMI (p=0.016) while patients with low MA had higher BMI (p=0.02) than patients with normal muscle. Baseline sarcopenia wasn’t associated with OS (p=0.231), PFS (p=0.541), and ORR (p=0.644). Also, MA wasn’t associated with OS (p=0.172), PFS (p=0.6) and ORR (p=1). No association was found with toxicities. Most commonly reported side effects were asthenia and HFS with Regorafenib, and neutropenia with TAS-102. 90% of patients had a dose reduction at second cycle of TAS-102, compared to 41.7% of patients treated with Regorafenib (p=0.031). 8/22 patients reported SML>5%: 6/12 patients in Regorafenib group, while 2/10 patients in TAS-102 group (p=0.204). 68.2% patients experienced muscle wasting, but SML wasn’t associated to OS (p=0.307) and ORR (p=0.781). One patient receiving TAS-102 experienced a 10.7% increase in muscle mass. Conclusion: Baseline sarcopenia, MA and SML during third-line therapy with Regorafenib or TAS102 did not influence survival, ORR and toxicities. SML>5% was more frequent in patients receiving Regorafenib, although the difference wasn’t statistically significant. These results must be interpreted with caution due to limited sample size.