Analysis of the relationship between body composition and the pharmacokinetics of panitumumab in the treatment of localized squamous cell carcinoma of the anus – An ancillary study of the FFCD0904 phase I and II trial

Cancer-related cachexia alters body composition (BC) and organ function, potentially affecting drug pharmacokinetics (PK).This ancillary study of the FFCD0904 phase I/II trial, which evaluated panitumumab -based radiochemotherapy in localized squamous cell carcinoma (SCC) of the anus, explored association between panitumumab PK, BC and its effects. Panitumumab PK parameters were estimated using a population PK approach. Pre-treatment CT scans at L3 were used to assess BC. Skin toxicity and efficacy data (tumor response, survival) were analyzed in relation to BC and PK parameters. Among 54 patients, 35 had panitumumab PK measurements, 42 had baseline CT scans, and 36 had skin toxicity data. In 25 patients with complete BC and PK data, AUC 0–14 and clearance (CL)tended to be positively correlated with body weight (BW, p = 0.0025 and 0.031), fat mass (FM, p = 0.027 and 0.033), and fat-free mass (FFM, p = 0.059 and 0.049),).Non-sarcopenic patients tended to show higher AUC 0–14 than sarcopenic patients (p = 0.0016). Lower albumin appeared to be associated with reduced clearance (p = 0.015). Despite these PK associations, neither BC nor panitumumab exposure seems correlated with tumor response, survival, or early skin toxicity. This exploratory analysis suggests that BW and BC may influence panitumumab PK, with patients who had lower BW, FM and FFM might have reduced exposure and clearance. Interpretation should be cautious due to the small sample size, confounding effect between BC and BW and potential disease-related effects. Larger studies with longitudinal BC and PK assessments are needed to clarify these relationships and guide dosing strategies.