Uptake of first-line immune checkpoint inhibitors among medically frail patients with advanced solid malignancies.

Abstract

e19316 Background: There are concerns about use of immune checkpoint inhibitor (ICI) therapy in medically frail patients, for whom ICIs do not have a proven survival or quality-of-life benefit. We compared uptake of first-line ICI treatment in routine practice between frail and non-frail patients with advanced solid malignancies. Methods: This retrospective cohort study used data from the Flatiron Health electronic health record-derived database. We included patients who started first-line systemic therapy from 2014 through 2018 for stage IV non-small cell lung cancer (NSCLC) without a targetable mutation, urothelial cell carcinoma (UCC), renal cell carcinoma (RCC), or hepatocellular carcinoma (HCC). We identified medically frail patients using literature-based criteria: Eastern Cooperative Oncology Group performance status (ECOG) ≥ 2, Elixhauser comorbidity index ≥ 3, or grade ≥3 liver or renal dysfunction as defined by NCI CTCAE v5. We used multivariable logistic regressions to examine associations between frailty and the probability of first-line use of an ICI-containing regimen (monotherapy or combination therapy), adjusted for age, insurance type, academic vs. community practice setting, type of cancer, and year of treatment. Results: Of 23,972 patients in the cohort, 17,122 (71.4%) were white, 10,237 (42.7%) were female, 9,666 (40.3%) were commercially-insured, and 13,144 (54.8%) met criteria for frailty. ICI use steadily increased over time in frail patients: among frail patients diagnosed in the last quarter of 2018, ICI-containing regimens represented 55% of first-line therapy starts in NSCLC; 35% in UCC; 55% in RCC; and 23% in HCC. Frail patients had a slightly higher likelihood of ICI use compared to non-frail patients (adjusted odds ratio [aOR] 1.12, 95% CI 1.04-1.20, p=0.002). This was primarily driven by greater use in patients with high comorbidity (aOR 1.15, 95% CI 1.08-1.23, p<0.001) (Table). Associations were consistent when examining first-line ICI monotherapy use only. Conclusions: First-line ICI use is common and increasing among frail patients with advanced solid malignancies. Prospective evidence is needed to assess the benefit (or lack thereof) of ICI use in medically frail patients. [Table: see text]