Survival Advantage Associated With Immune-Related Toxicity Reveals Racial Disparities in Solid Tumors

Danielle Ternyila

The study showed that the development of immune-related adverse events in advanced solid tumors was positively correlated with improved progression-free survival and overall survival in a retrospective analysis, which also showed that Caucasian patients developed immune-related adverse events more frequently than African American patients.

In immunotherapy clinical trials, minority groups are under-represented, highlighting a need for more inclusivity. As a start to revealing the difference in outcomes between patients from different racial groups, researcher conducted a retrospective review of data in patients with stage IV solid tumors. The study showed that the development of immune-related adverse events (irAEs) in advanced solid tumors was positively correlated with improved progression-free survival (PFS) and overall survival (OS) in a retrospective analysis, which also showed that Caucasian patients developed irAEs more frequently than African American patients.

The most common AE observed in this study was endocrine, which was observed in 40.7% of the study population. This was the first study to observe OS differences favoring endocrine irAEs and Caucasian patients. Study investigators noted that these factors may be surrogate markers of prognosis, but the validation of these results is needed in large-scale studies.

Overall, 293 patients met the eligibility criteria for this study, and 91 of these patients (31%) had irAEs of any grade. More irAEs were observed in the Caucasian patient population (60.4%) compared with the African American population (30.8%; P =.0141).

Survival advantages were observed in patients who experienced irAEs versus those with no irAEs. The median PFS for patients with irAEs was 5.8 months versus 3.0 months in those with no irAEs (P =.0088), and the median OS was 17.1 months versus 7.2 months (P =.0004), respectively.

Investigators noted, however, that these differences in OS and PFS were not observed in the Kaplan Meier analysis.

Overall, the study included 140 Caucasian patients (47.8%), 122 African American patients (41.6%), and 31 patients who were considered other (10.6%). Fifty-five Caucasian patients experienced irAEs (60.4%), 28 African Americans experienced irAEs (30.8%), and 8 other patients experienced irAEs (8.8%). The median PFS among those with irAEs was 7.7 months in the Caucasian population versus 5.8 months in the African American group and 2.2 months for other (P =.4601). The median OS among this group was 20.6 months for Caucasians, 12.9 months for African Americans, and 16.0 months for other racial groups (P =.0237).

Endocrine irAEs were observed in 23 Caucasian patients (62.2%), 13 African Americans (35.1%), and 1 other patient (2.7%). The median PFS in this group was 10.4 months for Caucasians, 5.2 months for African Americans, and 5.2 months for other (P =.2243). The median OS in those who experience endocrine irAEs was 21.8 months for Caucasians, 15.8 months for African Americans, and 6.2 months for other racial groups (P=.0356).

Out of 129 female and 164 male patients included in the study, 41 women experienced irAEs (45.1%) versus 50 men (54.9%). The median irAE PFS was 6.3 months in women versus 5.7 months in the men (P =.8977), and the median irAE OS was 16.3 months versus 18.5 months (P =.4756).

Endocrine irAEs were observed in 18 females (48.7%) and 19 males (51.4%), and the median endocrine irAE PFS was 7.7 months versus 5.7 months, respectively (P =.8542). The median endocrine irAE OS was 17.0 months for both women and men (P =.9495).

Investigators also evaluated the survival outcomes for patients who expressed PD-L1 greater than or less than 50%. For those with PD-L1 expression <50% (n = 69), 16 patients (17.6%) experienced irAEs, and for expression >50% (n = 32), 14 experienced irAEs, leading to a median PFS of 5.2 months versus 6.3 months, respectively (P =.6985). The median OS was 14.2 months for PD-L1 <50% versus 16.6 months for PD-L1 >50% (P = .6468).

Three patients with PD-L1 <50% had an endocrine irAE (25.0%) versus 9 patients with PD-L1 >50% (75.0%), and the median PFS was 5.3 months versus 6.3 months, respectively (P =1.000). The median OS for patients with PD-L1 expression <50% was 16.5 months versus 15.8 months for those with PD-L1 >50% (P =1.000).

The development of irAEs and its association to improved survival with treatment of immune checkpoint inhibitors is becoming evident in emerging data, the study authors said in their poster. Endocrine irAEs, in particular, are the most commonly reported toxicity, specifically in thyroid abnormalities. The objective of this study was to assess the incidence of irAEs, particularly endocrine irAEs, and its association with survival. The study also aimed to explore differences in survival based on race as minority groups are often under-represented in pivotal immunotherapy studies.

Patients with stage IV solid tumors who were treated with PD-1/PD-L1 inhibitors between January 2013 and December 2018 at MedStar Georgetown Cancer institute facilities were reviewed retrospectively. The differences in median PFS and OS were compared using the Wilcoxon rank-sum test. Kaplan-Meier methods with log-rank test for P value were also used to generate data on survival probability. Differences observed in median survival were stratified based on race and gender, as well as LDH and PD-L1 expression.

This study suggests race and endocrine irAEs may be possible surrogate markers for improved survival in patients with solid tumors. Conclusions regarding differences in survival probability cannot be made based on the significant heterogeneity observed in patients at baseline that results in discordant results between the 2 statistical tests.

Moving forward, a multivariate analysis can be conducted to further understand the patterns observed in this study. To validate these findings, a large pool of prospective data is required.

Reference

Pervali M, Gomes-Lima C, Tefera E, et al. Racial disparities in immune-related adverse events (irAE) of immune checkpoint inhibitors (ICPi) and association with survival based on clinical and biochemical responses. J Clin Oncol. 2020: 38 (suppl; abstr 7025). doi:10.1200/JCO.2020.38.15_suppl.7025