MON-303 - The Role of Type 1 Diabetes Development after PD-1 and PD-L1 Inhibitor Initiation as A Prognostic Factor for Survival Outcomes in Lung Cancer

Type 1 diabetes mellitus (T1D) is a rare but severe endocrine immune-related adverse event (irAE) linked to programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors. Although irAEs have been associated with improved survival in several malignancies, the relationship between Immune Checkpoint Inhibitor-induced diabetes (ICI-DM) and survival in lung cancer remains unclear. In this study, we examined the incidence of T1D occurring within the first year of PD-1/PD-L1 therapy in lung cancer patients and evaluated its association with survival outcomes, particularly during the early toxicity window, using drug-specific cohorts.

A retrospective cohort study was conducted using de-identified data from the TriNetX Research Network. 152, 775, 371 patients across 112 healthcare organizations were included. We identified adults aged 18 or older with lung and bronchus neoplasms and patients with ICI-DM. We then identified the four most commonly used PD-1 and PD-L1 inhibitors in Lung Cancer associated with endocrine adverse effects, namely Pembrolizumab, Nivolumab, Atezolizumab, and Durvalumab. We considered early toxicity as T1D diagnosed within 90 days of immunotherapy initiation. Kaplan-Meier analysis assessed overall survival. Statistical comparisons of survival rates between groups were performed using the log-rank test. Propensity matching was used to adjust for age, sex, comorbidities, and lines of treatment.

Among patients with lung cancer, 341 of 35,267 (0.09%) on Pembrolizumab, 141 of 13,617 (0.01%) on Nivolumab, 93 of 10,113 (0.09%) on Durvalumab, and 104 of 9,462 (0.01%) on Atezolizumab developed T1D after initiation of immunotherapy. The population was predominantly white males. After propensity matching, those who were initiated on Pembrolizumab, Atezolizumab, or Durvalumab and developed T1D did not show a significant difference in survival outcomes compared with those who did not develop T1D. In contrast, the nivolumab cohort demonstrated significantly prolonged median survival among patients who developed T1D (1,212 vs 392 days; p≈0.01). This finding is consistent with broader irAE–survival associations but should be interpreted cautiously due to small event counts. Early or late toxicity did not affect overall survival for any immunotherapy medication.

Unlike thyroid irAEs, T1D is an infrequent irAE and was not associated with a clear survival advantage in patients treated with pembrolizumab, atezolizumab, or durvalumab, regardless of the timing of toxicity. The contrast between strong thyroid irAE survival associations and weaker T1D signals underscores the need for organ-specific rather than aggregated analyses of endocrine irAEs because not all endocrine toxicities convey equivalent prognostic information.

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