Early endocrine diagnoses and subsequent survival after immune checkpoint inhibitor initiation in non-small cell lung cancer: a 180-day landmark cohort study.

BACKGROUND

Endocrine diagnoses newly recorded after immune checkpoint inhibitor (ICI) initiation may be associated with subsequent outcomes, but time-dependent bias and the limitations of diagnosis-code attribution complicate interpretation.

METHODS

We conducted a retrospective 180-day landmark cohort study using a federated electronic health record network. Patients with non-small-cell lung cancer (NSCLC) initiating ICI were classified according to the presence or absence of a newly recorded qualifying thyroid, pituitary, or adrenal diagnosis during days 1-180 after first ICI. Both cohorts excluded qualifying endocrine diagnoses during days -365 to -1 and required a recorded visit during months 5-6. After 1:1 propensity-score matching, 7,696 patients were included in each group. Outcomes were assessed from day 181.

RESULTS

Newly recorded endocrine diagnoses were associated with lower subsequent mortality (hazard ratio [HR], 0.782; 95% confidence interval [CI], 0.745-0.821; P < 0.0001) and a lower hazard of first recorded prespecified subsequent systemic therapy or death in an independently matched analysis (HR, 0.849; 95% CI, 0.773-0.934; P = 0.0007). Exploratory severe infection (HR, 1.255; 95% CI, 1.151-1.369) and healthcare utilization (HR, 1.055; 95% CI, 1.013-1.099) outcomes occurred more frequently in the exposed group. Findings were directionally consistent across subgroup and sensitivity analyses, including a repeat-code definition.

CONCLUSIONS

Among patients satisfying the 180-day landmark and observability criteria, newly recorded endocrine diagnoses after ICI initiation were associated with lower subsequent mortality. This association is conditional on the specified landmark and observability criteria and does not establish ICI attribution, causality, or prediction of comparative treatment benefit.