Durvalumab After Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer: Inferior Outcomes and Lack of Health Equity in Hispanic Patients Treated With PACIFIC Protocol (LA1-CLICaP)

Abstract

ObjectivesTo compare the rate disparity between outcomes (overall survival (OS), progression-free survival (PFS), and safety) of concurrent chemoradiation (cCRT) followed by durvalumab in two patient cohorts with locally advanced (LA) stage III non-small cell lung cancer (NSCLC), one non-Hispanic White (NHW), and the other Latin-American.MethodsA multicenter retrospective study was performed, including 80 Hispanic and 45 NHW LA stage III NSCLC patients treated with cCRT followed by durvalumab. Both cohorts were analyzed in terms of main outcomes (OS, PFS, and safety) and compared between them and with the PACIFIC trial population outcomes. The efficacy-effectiveness gap was assessed using an efficacy-effectiveness (EE) factor that was calculated by dividing each cohort median overall survival by the corresponding reference OS from the PACIFIC trial. In both cohorts, results of PD-L1 testing were recorded, and the main outcomes were compared according to PD-1 expression levels (≥50%, 1–49%, and <1%).ResultsFor the entire population (N=125), the overall response rate (ORR) was 57.6% (N=72), and 18.4% (N=25) achieved stable disease. OS was 26.3 months (95%CI 23.9-28.6), and PFS was 20.5 months (95%CI 18.0-23.0). PFS assessed by ethnicity showed a median for the Hispanic population of 19.4 months (95%CI 16.4-22.5) and 21.2 months (95%CI 17.2-23.3; p=0.76) for the NHW group. OS by race showed a significant difference in favor of the NHW group, with a median OS of 27.7 months (95%CI 24.6-30.9) vs. 20.0 months (95%CI 16.4-23.5) for Hispanics. (P=0.032). Unadjusted 12-month and 24-month OS was 86.6% (95%CI 79.9–88.0) and 46.6% (95%CI 40.2–48.3) for NHW compared to 82.5% (95%CI 77.1–84.2) and 17.5% (95%CI 15.6-24.5) in Hispanics. NHW had an EE factor of 0.78 and Hispanics had 0.58, showing a reduction in survival versus NHW and PACIFIC of 20% and 42%, respectively. HR for the OS among NHWs and Hispanics was 1.53 (95%CI 1.12-1.71; P=0.052) and 2.31 (95%CI 1.76-2.49; P=0.004). Fifty-six patients (44.8%) had some degree of pneumonitis due to cCRT plus durvalumab. There was no difference in the proportion of pneumonitis according to race (P=0.95), and the severity of pneumonitis was not significantly different between Hispanics and NHWs (P=0.41).ConclusionsAmong patients with LA stage III NSCLC, NHW had better survival outcomes when compared to Hispanics, with an OS that seems to favor the NHW population and with an EE factor that shows a shorter survival in Hispanics compared with NHW and with the PACIFIC trial group.

Efficacy of consolidation of immune checkpoint inhibitor after chemoradiation for unresectable, locally advanced PD‑L1 negative non‑small cell lung cancer: A systematic review and meta‑analysis

“…A total of 527 studies were obtained after searching the aforementioned databases. A total of 23 studies were included following screening of abstracts and full texts according to the selection criteria [Durm et (30)]. Among these, 16 were included in part one, and 15 were included in part two.…”

Lung Cancer Clinical Trials in Latin America in the Era of Cooperative Groups: A 20-Year Analysis

“… 19 Thus, the generalizability of lung cancer clinical trial data to Hispanic and Latin American populations merits further investigation. The need for further population-specific investigations is highlighted by a poignant example from the study by Raez et al, 8 who reported differential survival outcomes in Hispanic population compared with non-Hispanic White population who were treated using the PACIFIC protocol. Therefore, in the current state of lung cancer clinical trials, it remains unclear if data from non-LA trials can be appropriately generalized to patients with lung cancer in Latin America.…”

“… 2 , 3 Despite these barriers, lung cancer researchers in Latin America have published findings highlighting region-specific trends in lung cancer epidemiology, differential resource utilization, and survival responses to lung cancer treatments, thus highlighting the need for increased efforts in lung cancer research in this region. 4 - 8 Of particular interest, Latin American cancer specialists have advocated for increased participation in lung cancer clinical trials as a vehicle for driving forward regional cancer research. 9 - 11 …”

“…2,3 Despite these barriers, lung cancer researchers in Latin America have published findings highlighting regionspecific trends in lung cancer epidemiology, differential resource utilization, and survival responses to lung cancer treatments, thus highlighting the need for increased efforts in lung cancer research in this region. [4][5][6][7][8] Of particular interest, Latin American cancer specialists have advocated for increased participation in lung cancer clinical trials as a vehicle for driving forward regional cancer research. [9][10][11] To begin addressing these barriers in cancer research, multinational oncology cooperative groups (OCGs) such as the Latin American Consortium for the Investigation of Lung Cancer (CLICaP, organized in 2011) and the Latin American Cooperative Oncology Group (LACOG, organized in 2009) were founded.…”

Diversity and Disparities in Lung Cancer Outcomes Among Minorities

“…Raez et al 38 compared the clinical outcomes (PFS and OS) of 80 Hispanic patients with 45 NHW patients diagnosed with unresectable stage III NSCLC in 5 community/academic centers treated according to PACIFIC trial (chemotherapy concomitant with radiation followed by maintenance with durvalumab). 38,39 For the entire population (N = 125), the overall response rate was 57.6%, OS was 26.3 months, and PFS was 20.5 months. Progression-free survival assessed by ethnicity showed a median for the Hispanic population of 19.4 versus 21.2 months for the NHW group.…”