Muscle Loss During First-Line Chemotherapy Impairs Survival in Advanced Pancreatic Cancer Despite Adapted Physical Activity.

Background: Advanced pancreatic ductal adenocarcinoma (aPDAC) is often accompanied by significant muscle mass loss, contributing to poor prognosis. SarcAPACaP, an ancillary study of the GERCOR-APACaP phase III trial, evaluated the role of adapted physical activity (APA) in aPDAC Western patients receiving first-line chemotherapy. The study aimed to assess (1) the potential impact of computed tomography (CT)-quantified muscle mass before and during treatments on health-related quality of life (HRQoL) and overall survival (OS) and (2) the role of APA in mitigating muscle mass loss.

Methods: In the APACaP trial, aPDAC patients with ECOG performance status (PS) 0-2 were randomized 1:1 to usual care including first-line chemotherapy or usual care plus a 16-week home-based APA program. In the SarcAPACaP study, the surface muscular index (SMI) was determined from L3 CT scan slices. Two patient populations were analysed: those with CT scan available at baseline (modified[m] intent-to-treat [ITT]1-W0) and those with CT scans available at both W0 and W16 (mITT2 W0-W16). Low muscle mass was defined by low SMI with SMI < 41 cm/m for women and < 43 and < 53 cm/m for men with body max index < 25.0 and ≥ 25.0 kg/m, respectively. Muscle loss was defined by the relative difference of SMI between W0 and W16 (100*[SMI W16-SMI W0]/SMI W0). In mITT2 W0-W16, patients were stratified into three groups based on the severity of muscle loss: none, moderate (0%-10%) and high (≥ 10%). Associations between muscle mass loss and OS, time until definitive deterioration (TUDD) of HRQoL and the effect of APA on loss of muscle mass were assessed.

Results: Between October 2014 and May 2020, 313 patients were prospectively enrolled, with 225 in mITT1 W0 and 128 in mITT2 W0-W16, with 65 assigned to the APA arm. Both groups had similar baseline characteristics with comparable OS and TUDD. A low SMI at W0 was not associated with OS and TUDD of HRQoL in either group. Among mITT2 W0-W16 patients, high muscle mass loss (n = 27) independently predicted OS (p = 0.012) and showed a trend toward negatively affecting TUDD of HRQoL. Notably, APA did not mitigate muscle loss in our study population.

Conclusions: Longitudinal muscle mass loss emerged as a predictive factor for both OS and HRQoL in aPDAC patients undergoing chemotherapy, while a low SMI at diagnosis did not provide prognostic value. APA did not impact muscle mass loss in this population.