In a retrospective cohort study reported in The Lancet Oncology, Miller et al found that ICI treatment for cancer had similar efficacy and reduced toxicity in Black patients vs White patients in the U.S. Veterans Health Administration (VHA) system.
As stated by the investigators, “Black patients were severely under-represented in the clinical trials that led to the approval of … [immune checkpoint inhibitors] for all cancers. The aim of this study was to characterise the effectiveness and safety of [immune checkpoint inhibitors] in Black patients.”
Study Details
The study involved VHA system data on non-Hispanic Black or African American (Black) or non-Hispanic White (White) patients who received PD-1, PD-L1, CTLA-4, or LAG-3 inhibitors between January 1, 2010, and December 31, 2023. A random sample of patients matched for baseline characteristics was used to evaluate comparative toxicity.
Key Findings
A total of 26,398 patients were included in the analysis: 4,943 (18.7%) were Black, 21,455 (81.3%) were White, 895 (3.4%) were female, 25,503 (96.6%) were male, 11,859 (45%) had non–small cell lung cancer, and 26,045 (98.7%) received PD-1 or PD-L1 inhibitors.
At data cutoff (in August 2024), median follow-up was 40.3 months among Black patients and 43.9 months among White patients. At 2 years: 10.7% (95% confidence interval [CI] = 9.8%–11.7%) of Black patients vs 8.6% (95% CI = 8.2%–9.0%) of White patients had discontinued treatment (adjusted hazard ratio [HR] = 0.91, 95% CI = 0.87–0.95, P < .0001); 23.5% (95% CI = 22.3%–24.8%) of Black patients vs 25.6% (95% CI = 25.0%–26.2%) of White patients had started a new treatment (adjusted HR = 1.00, 95% CI = 0.95–1.05, P = .96); and overall survival was 36.5% (95% CI = 35.2%–38.1%) for Black patients vs 36.5% (95% CI = 35.8%–37.1%) for White patients (adjusted HR = 0.95, 95% CI =0.90–0.99, P = .036).
At 2 years among the sample of 862 Black patients and 848 White patients in the safety analysis: any-grade immune-related adverse events (irAEs) occurred in 33.1% vs 44.1% (adjusted HR = 0.75, 95% CI = 0.62–0.90, P = .0026); immune-related adverse events requiring systemic steroids occurred in 15.0% vs 22.6% (adjusted HR = 0.61, 95% CI = 0.46–0.81, P = .0005; and immune-related adverse events resulting in permanent discontinuation of immune checkpoint inhibitor therapy occurred in 14.6% vs 21.7% (adjusted HR = 0.58, 95% CI = 0.44–0.78, P = .00024).
An exploratory analyses of immune-related adverse event subtypes showed significant risk reductions in Black patients for colitis (HR = 0.46, P = .0026) and hyperthyroidism or hypothyroidism (HR = 0.63, P = .011).
The investigators concluded: “Compared with White patients, Black patients had similar [immune checkpoint inhibitor] effectiveness and lower toxicities among those treated in the national VHA system, potentially reflecting an important difference in the therapeutic ratio (ratio of benefit to harm) of [immune checkpoint inhibitors]. Our findings of decreased toxicity among Black patients require further investigation to assess their generalisability.”
Alex K. Bryant, MD, MAS, of the Department of Radiation Oncology, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the Million Veteran Program, Office of Research and Development, Veterans Health Administration and the LUNGevity foundation. For full disclosures of the study authors, visit thelancet.com.
