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

Abstract

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 cm²/m² for women and < 43 and < 53 cm²/m² for men with body max index < 25.0 and ≥ 25.0 kg/m², 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.