Early functional deterioration during first-line ICI-based therapy in advanced NSCLC: implications for supportive care

To compare objective functional measures for identifying early functional deterioration during first-line ICI-based therapy in advanced NSCLC and explore their relevance for supportive-care monitoring.

This secondary exploratory analysis used prospectively collected data from a randomized trial of pulmonary rehabilitation. Forty-two participants with baseline and 8-week assessments were evaluated using quadriceps force, SPPB, and 6MWD. Early deterioration was defined as decline in at least one domain. Deterioration frequency, cross-domain agreement, baseline associations, and subsequent PFS were examined, accounting for randomized treatment allocation.

Under the primary operational definitions, deterioration in at least one functional domain occurred in 29/42 participants (69.0%) despite stable ECOG performance status. Deterioration affected quadriceps force in 23 (54.8%), SPPB in 14 (33.3%), and 6MWD in 5 (11.9%); 16 participants deteriorated in one domain and 13 in two. Frequencies differed significantly across measures (Cochran's Q=16.76, p<0.001), with low pairwise agreement. No examined baseline characteristic was significantly associated with deterioration after adjustment for PR/UC allocation. Participants with deterioration had numerically less favorable subsequent PFS, but the association was not statistically significant.

Early functional deterioration during first-line ICI-based therapy was common and heterogeneous across domains. Repeated objective assessment across complementary functional measures may help identify emerging functional vulnerability and support timely individualized supportive-care evaluation.