Impact of sarcopenia (S) on efficacy and toxicity of nivolumab (N) in patients (pts) with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) in TOPNIVO (T) study

N is the standard of care in pts with platinum refractory (PR) R/M HNSCC, but no validated markers to predict efficacy are available. S is a clinical condition characterized by loss of strength and muscle mass. In this study, we evaluated the prognostic role of skeletal muscle index (SMI) in the population of the T study. T was a single-arm, phase II trial in which 343 pts with PR R/M HNSCC treated with N (3 mg/kg, Q2W) were included between 08/2017 and 11/2018. SMI was estimated at the third lumbar vertebra using the mean value of two consecutive CT-scan images, at pre-baseline (P-B; 1-4 months before inclusion) and at baseline (B). Skeletal muscle was identified with Hounsfield Unit thresholds (–29 to +150). S was defined as SMI <52.4 cm2/m2 for men and <38.5 cm2/m2 for women. We evaluated whether S and the relative evolution of SMI between P-B and B have an impact on overall response rate (ORR), progression-free survival (PFS), overall survival (OS) and grade ≥ 3 adverse events (AEs), using Cox models and logistic models adjusted for clinical prognostic factors. 253 pts were evaluated for SMI. 82% were men, median age was 62 years (range 32-87). ECOG performance status was 0 in 26%, 1 in 60% and 2 in 14%. 201 (79%) pts were sarcopenic at B, more frequently in men (87%) than in women (43%). No significant difference of ORR (p=0.98), PFS (p=0.69), OS (p=0.41) and grade ≥ 3 AEs (p=0.36) were observed between sarcopenic and non-sarcopenic patients. 77 P-B CT-scans were available. The median value of relative evolution of SMI between P-B and B was -0.95% per month (range -12.1%;+8.9%). 25 (32%) pts had a relative evolution ≤ -2%/month. Relative evolution ≤ -2%/month was not significantly associated with ORR (p=0.28), PFS (p=0.58) and OS (p=0.35). It seems to have an impact on the occurrence of severe AEs (p=0.04): 88% of pts with SMI evolution ≤ -2%/month had severe AEs versus 57.7% of pts with evolution > -2%/month. In the T population, sarcopenia evaluated by SMI did not showed a prognostic role on tumor response, PFS and OS. Muscle strength was not studied. Pts with great decrease of SMI during the few months before treatment had a greater incidence of grade ≥ 3 AEs.