Association between PD ‐1 inhibitor‐related adverse events and frailty assessed by frailty index in lung cancer patients

BACKGROUND: The programmed cell death protein 1 (PD-1) inhibitor, as one of the immune checkpoint inhibitors (ICIs), is the standard treatment for advanced lung cancer. However, immune-related adverse events (irAEs) remain poorly understood toxicities. It is unclear whether frailty plays a role in the occurrence of irAEs. Thus, we assess whether irAEs occur more often in frail patients than in non-frail patients according to the Frailty Index (FI). METHODS: A retrospective study was conducted. Medical records from lung cancer patients treated with PD-1 inhibitors (Sintilimab, Camrelizumab, Tislelizumab, and Pembrolizumab) at Peking University First Hospital (May 2018-June 2022). Patients were categorized into non-frail and frail groups according to a cut-point of 0.25 by FI. The FI calculation included 28 baseline variables, all of which were health deficits measured by questionnaires and body measurements. RESULTS: The statistical analysis included 114 advanced lung cancer patients. The median age was 66 years, and the male/female ratio was 4.7:1 (94/20). Approximately 39 (34%) were classified as frail. PD-1 inhibitor-related adverse events occurred in 17.5% of patients, and 6.1% experienced irAEs of grade ≥3. There was no significant difference in the occurrence of irAEs (14.7% vs. 23.1%, p = 0.26), grade ≥ 3 irAEs (5.3% vs. 7.7%, p = 0.93), and treatment discontinuation due to irAEs (12.0% vs. 17.9%, p = 0.39) between non-frail and frail patients. However, frail patients are more likely to have more than one type of irAEs and are more possibly to have checkpoint inhibitor pneumonitis (CIP) than non-frail patients when they use PD-1 inhibitors (p < 0.05). Frail patients had a longer hospital stay (6 vs. 3 days, p = 0.01). CONCLUSIONS: Frailty is not associated with severe irAEs, but is related to CIP. Meanwhile, it predicts more than one type of irAEs and a longer hospital stay. Frailty screening has added value to the decision-making process for frail patients eligible for PD-1 inhibitors.