(063) Identifying the Period of Heightened Risk for Adrenal Insufficiency in Patients with Advanced Non-Small Cell Lung Cancer Treated with First-Line Immune Checkpoint Inhibitors

Background: Immune checkpoint inhibitors (ICIs) have become standard of care in patients with first-line (1L) advanced non-small cell lung cancer (aNSCLC); however, immune mediated adverse events (imAEs) pose a significant safety concern. Endocrine imAEs, such as thyroid dysfunction and particularly adrenal insufficiency (AI), are concerning imAEs related to ICI-treated aNSCLC pts as these are permanent, requiring potential life-long hormone replacement therapy. Identifying periods of heightened risk for AI may allow for enhanced monitoring and subsequent expeditious treatment.

Objectives: To identify the periods of highest risk for AI among aNSCLC patients treated with 1L PD-(L)1 inhibitors, as monotherapy and in combination with chemotherapy.

Methods: Patients (≥18 years) with aNSCLC initiating 1L treatment with anti-PD-(L)1 immunotherapy between 24 October 2016 and 31 July 2022 were retrospectively identified using the ConcertAI Oncology Dataset. Incident AI was captured from ICI initiation (index) until the earliest of: AI diagnosis, death, last EHR activity, new line of therapy, 90 days without treatment, or end of study period (31 October 2022). AI diagnoses were captured using either ICD-10 codes (ie, E27.1-E27.4x) or MedDRA preferred terms associated with a sentinel event (ie, death, ED visit, hospitalization, medication change, therapy discontinuation, or radiotherapy stop). and summarized using cumulative incidences at 6, 9, and 12 months, and incidence rates during distinct time periods (0-6, 7-9, 10-12, and 13+ months) of follow-up.

Results: For aNSCLC patients treated with anti-PD-(L)1 immunotherapy (N=4,776), the cumulative incidence of AI was 1.0% (95% CI: 0.7%-1.4%) at 6 months, 1.8% (95% CI: 1.3%-2.4%) at 9 months, and 2.3% (95% CI: 1.6%-2.9%) at 12 months. Patients treated with combination therapy tended to have a greater risk of AI by 12 months compared to monotherapy patients (2.6% [95% CI: 1.7%-3.5%] versus 1.8% [95% CI: 0.8%-2.7%]), as well as those receiving systemic steroids or immunosuppressives prior to or at ICI initiation compared to those without (4.6% [95% CI: 1.8%-7.4%] versus 1.9% [95% CI: 1.3%-2.5%]). Incidence rates of AI were 5.84, 8.94, 4.41, and 2.51 per 100,000 person-days at 0-6, 7-9, 10-12, and 13+ months after ICI initiation.

Conclusions: This study demonstrated a high incidence of AI among aNSCLC patients treated with ICIs within the first 12 months of treatment, and most notably between 7-9 months after ICI initiation. Patient subgroups at greatest risk for AI include those treated with combination therapy and those receiving systemic steroids or immunosuppressives.