P-354A multicenter non-interventional study exploring the impact of sarcopenia on the outcomes of colorectal cancer patients treated with chemotherapy plus bevacizumab – avawatchers

Introduction: Low muscle mass or sarcopenia is an independent predictor of immobility, comorbidity and mortality. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and function (strength and/or performance) and it is firmly correlated with physical disability, poor quality of life and death. Several mechanisms are known to explain sarcopenia (inflammation, neurodegenerative process, hormonal disorders, lack of exercise, malnutrition). While there is a high prevalence in the elderly, it can also develop in younger adults, especially in advanced cancer. Gradual loss of muscle mass during cancer treatment occurs in more than half of the patients. Multiple studies demonstrated patients with sarcopenia to be more prone to toxic effects of chemotherapy, cancer related fatigue and/or nosocomial infections, leading to dose reductions or treatment delays, which potentially reduce treatment efficacy and is associated with worse outcome and mortality. This study will investigate whether sarcopenia is predictive for a worse progression free survival and increased treatment related toxicity in patients with metastatic colorectal cancer (mCRC). Methods: Trial design: This multicenter non-interventional study includes patients with mCRC who received 1st line chemotherapy plus bevacizumab and who are considered eligible to continue chemotherapy plus bevacizumab beyond first progression and who are willing and able to comply with the procedures of the protocol (n = 200). The higher incidence of sarcopenia after an initial period of cancer therapy prompted the enrolment after first progression, allowing retrospective 1st line and prospective 2nd line data capture. Including only patients receiving bevacizumab beyond progression confines fluctuations in treatment related toxicity, potentially reducing bias on study parameters. The primary endpoint is to assess the impact of the presence of CT-scan based sarcopenia at study entry (SE) on the time to second progression (PFS2). CT based sarcopenia is defined as a lumber (L3) skeletal muscle index below the level of 41 cm2/m2 for women and 43 or 53 cm2/m2 for men with a BMI below or above 25 respectively. Secondary endpoints include the relation between the presence of sarcopenia at SE and time to first progression (PFS1), patient and disease characteristics at initial diagnosis, functional (FACT-C), physical (muscle strength, BMI) and nutritional status (PG-SGA,VAS for appetite) and treatment-related toxicity (MDASI). Safety monitoring includes the recording of bevacizumab and sarcopenia-related adverse events. The primary endpoint will use Kaplan-Meier survival analysis. Estimates and 95% confidence intervals will be calculated for the median PFS2 and the 1st and 3rd quartiles. The 2 populations (sarcopenic versus non-sarcopenic at study entry) will be compared by means of a log-rank test, performed two-sided at the 0.05 level of significance. Clinical trial registration: ClinicalTrials.gov NCT02673710 Results: NA (Trial in Progress) Conclusion: NA (Trial in Progress)