Analysis of Real-World Data to Investigate the Impact of Race and Ethnicity on Response to Programmed Cell Death-1 and Programmed Cell Death-Ligand 1 Inhibitors in Advanced Non-Small Cell Lung Cancers

Abstract

Background. Racial disparities among clinical trial participants present a challenge to assess whether trial results can be generalized into patients representing diverse races and ethnicities. The objective of this study is to evaluate the impact of race and ethnicity on treatment response in advanced non-small cell lung cancer (aNSCLC) patients treated with PD-1 or PD-L1 inhibitors through analysis of real-world data (RWD). Materials and Methods. A retrospective cohort study of 11,138 lung cancer patients treated at hospitals within the Mount Sinai Health System was performed. Patients with confirmed aNSCLC who received anti-PD1/PD-L1 treatment were analyzed for clinical outcomes. Our cohort included 249 aNSCLC patients who began nivolumab, pembrolizumab, or atezolizumab treatment between November 2014 and December 2018. Time-to-treatment discontinuation (TTD) and overall survival (OS) were the analyzed clinical endpoints. Results. After a median follow-up of 14.8 months, median TTD was 7.8 months (95% confidence interval 5.4not estimable [NE]) in 75 African American patients vs. 4.6 (2.4 -7.2) in 110 White patients (hazard ratio [HR] 0.63). Median OS was not reached (18.4 -NE) in African Americans vs. 11.6 months (9.7 -NE) in Whites (HR 0.58). Multivariable cox regression conducted with potential confounders confirmed longer TTD (adjusted HR 0.65) and OS (adjusted HR 0.60) in African American vs. White patients. Similar real-world response rate (42.6% vs. 43.5%) and disease control rate (59.6% vs. 56.5%) were observed in the African American and White patient populations. Further investigation revealed the African American group had lower incidence (14.7%) of putative hyperprogressive diseases (HPD) upon anti-PD1/PD-L1 treatment than the White patient group (24.5%). Conclusions. Analysis of RWD showed longer TTD and OS in African American aNSCLC patients treated with anti-PD1/PD-L1 inhibitors. Lower incidence of putative HPD is a possible reason for the favorable outcomes in this patient population. The Oncologist 2021;9999:• • Implications for Practice: There is a significant underrepresentation of minority patients in randomized clinical trials, and this study demonstrates we can use real world data to investigate the impact of race and ethnicity on treatment response. In retrospective analysis of advanced non-small cell lung cancer patients treated with PD-1 or PD-L1 inhibitors, African American patients had significantly longer time-to-treatment discontinuation and longer overall survival. Analysis of realworld data can yield clinical insights and establish a more complete picture of medical interventions in routine clinical practice.

Hyperprogressive disease in patients suffering from solid malignancies treated by immune checkpoint inhibitors: A systematic review and meta-analysis

“…Illustrated by Figure 8 , a significant discrepancy was found among the five subgroups ( P = .02). The pooled incidence of HPD was 16.2% in patients suffering from gastrointestinal (GI) tract cancer ( n = 5, 95% CI, 10.4%–24.1%) ( 33 , 45 , 56 , 57 , 60 ); 14.4% in patients with NSCLC ( n = 14, 95% CI, 12.2%–17.0%) ( 13 , 16 , 17 , 21 , 29 , 34 , 42 – 44 , 51 , 54 , 59 , 62 , 63 ), 9.9% in patients with melanoma ( n = 3, 95% CI, 1.6%–43.4%) ( 35 , 36 , 53 ); 10.8% in patients with HCC ( n = 4, 95% CI, 8.4%–13.8%) ( 14 , 39 , 40 , 61 ); 18.06% in patients with HNC ( n = 6, 95% CI, 15.0%–21.6%) ( 15 , 37 , 38 , 48 , 49 , 52 ). Significant differences were found between these five tumor types (Q = 11.16, P = .0248), indicating that tumor type is a source of heterogeneity.…”

Benefit and toxicity of programmed death-1 blockade vary by ethnicity in patients with advanced melanoma: an international multicentre observational study

“…Our finding corroborates those of earlier studies demonstrating ethnic differences observed in patients treated with anti-PD-1 monotherapy for advanced non-small cell lung cancer. 51 Interestingly, this association of ethnicity and clinical benefit did not hold in acral, mucosal and uveal melanomas. This observation contradicts the prevailing notion that associations between the efficacy of PD-1 blockade and ethnicity are due solely to differences in the prevalences of melanoma subtypes.…”

Comparison of Treatment Efficacy and Survival Outcomes Between Asian and Western Patients With Unresectable Gastric or Gastro-Esophageal Adenocarcinoma: A Systematic Review and Meta-Analysis

“…From our perspective, the development of new hallmarks for predicting responses to immunotherapy must take into account the unique immunogenomic features that Asian and Western patients do not share ( 39 , 40 ). As immune checkpoint inhibitors play an increasingly critical role in the treatment of multiple advanced cancers, the correlation between geographic locality and treatment responses warrants further investigations ( 41 ).…”