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Angelica D'Aiello
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P09 - Health Services Research/Health Economics - Real World Outcomes (ID 121)
- Event: WCLC 2020
- Type: Posters
- Track: Health Services Research/Health Economics
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P09.03 - Thyroid Dysfunction in Lung Cancer Patients Treated With Immune Checkpoint Inhibitors (ICI): Outcomes in a Multiethnic Urban Cohort. (ID 1279)
00:00 - 00:00 | Presenting Author(s): Angelica D'Aiello
- Abstract
Introduction
It is unclear how variables such as race, gender, and concurrent chemotherapy relate to the development and evolution of immune-related adverse effects (irAE) in patients receiving ICI. We sought to characterize thyroid dysfunction and its relationship with progression-free survival (PFS) in a multiethnic cohort of lung cancer patients treated with ICI.
Methods
A retrospective chart review of lung cancer patients receiving an anti-PD1 or PD-L1 agent from January 2016 to July 2019 was performed. Subjects included had normal baseline thyroid function. Thyrotoxicosis and hypothyroidism were defined as thyroid-stimulating hormone level less than 0.4 and greater than 4.6, respectively. Time-to-event analysis with inverted Kaplan Meier curves and log-rank tests were used to compare thyroid dysfunction among race, gender, and treatment subgroups. Multivariate Cox proportional hazards models were fitted to compare time-to-thyroid dysfunction among race subgroups controlling for age, gender, treatment type and duration. PFS at 24 weeks among thyroid dysfunction subgroups was compared using Kaplan Meier curves and log-rank tests.
Results
We identified 206 subjects including 76 who went on to develop thyroid dysfunction. Rates of thyroid dysfunction by one year occurred at similar frequencies among all races (p=0.92). Thyrotoxicosis occurred at significantly higher rates in Black (25, 31.6%) than in White (7, 16.7%) and Hispanic (8, 12.7%) subjects (p=0.02). In contrast, hypothyroidism occurred more often in White (13, 31.0%) and Hispanic (18, 28.6%) than in Black (12, 15.2%) subjects (p=0.09). Gender and concurrent chemotherapy showed no significant association with thyroid dysfunction (p=0.81 and p=0.67, respectively). Multivariate Cox regression also showed significantly higher rates of thyrotoxicosis in Black subjects (HR 0.380, p=0.019), and hypothyroidism in White (HR 2.28, p=0.04) and Hispanic subjects (HR 1.2, p=0.037). For subjects with thyrotoxicosis (N = 42) and hypothyroidism only (N = 28), median onset was 6.0 weeks (2.49-44.8) and 10.0 weeks (1.3-37.0), respectively. Fourteen subjects experienced thyrotoxicosis followed by hypothyroidism. Among subjects with thyrotoxicosis, only one required treatment with methimazole. Of subjects with hypothyroidism (N = 48), 40.0% (N = 19, 9.2% of total cohort) received treatment with levothyroxine. Other irAE were observed in 11.2% (N = 23) of subjects, including pneumonitis (10, 4.9%), dermatitis (8, 3.9%), colitis (2, 1.0%), inflammatory arthritis (2, 1.0%), and nephritis (1, 0.5%). The majority of irAE occurred in subjects receiving ICI alone (16, 69.6%) versus concurrent chemotherapy (7, 30.4%). Of subjects with thyroid dysfunction (N = 76), other irAE co-occurred in 11.8% (N = 9). PFS was similar among subjects with and without thyroid dysfunction by chi-square (p=0.32) and log-rank test (p=0.35).
Conclusion
PFS was similar among subjects with and without ICI-related thyroid dysfunction. Despite the anticipated immunosuppressive effect of chemotherapy and influence of gender, neither correlated with thyroid dysfunction; however, race did. Black subjects exhibited significantly higher rates of thyrotoxicosis. These results echo prior research showing that non-ICI-related thyrotoxicosis, including Graves’ disease, occurs more often in Blacks. While the pathogenesis of ICI-related thyroid dysfunction as compared to other irAE is unclear, the role of race demonstrated by our study warrants further investigation.
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P33 - Pathology - Immunotherapy Biomarker (ID 101)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P33.09 - Tumor Mutational Burden in Advanced Non-Small Cell Lung Cancer Treated with Immunotherapy: Outcomes in a Multiethnic Cohort (ID 3759)
00:00 - 00:00 | Author(s): Angelica D'Aiello
- Abstract
Introduction
Immune check point inhibitors (ICI) provide clinical benefit for a subset of patients with non-small cell lung cancer (NSCLC). Identifying those patients most likely to respond to ICI-based regimens is a priority given the potential for toxicity and costs of these therapies. Tumor mutational burden (TMB), the number of somatic mutations in a tumor and a surrogate for a tumor neoantigens, has emerged as a potential predictor to ICI responses. There is lack of data assessing the link between TMB and response to ICI in minority populations. We assessed the association of TMB with survival outcomes in a predominantly Hispanic and Black population with advanced NSCLC treated with ICI.
Methods
We retrospectively analyzed patients with stage IV NSCLC who underwent Foundation one (F1) next generation sequencing assay and were treated with first-line ICI, with or without concurrent chemotherapy, at Montefiore Einstein Cancer Center from 2014 to 2020. Demographic, clinicopathological, and treatment characteristics were obtained from electronic medical records. TMB was obtained from F1 reports and was categorized as TMBlow (<10 mut/Mb) and TMBhigh (=>10 mut/Mb). ICI included anti-PD1 and anti-PD-L1 agents. Progression-free survival (PFS) was calculated from ICI start to the date of clinical or radiographic evidence of disease-progression prompting treatment change or cancer-related death, whichever occurred first. Overall survival (OS) was calculated from ICI initiation to the date of death from any cause. PFS or OS by TMB status was assessed using Kaplan-Meier curves and log-rank tests. A p-value of <0.05 was considered significant.
Results
We identified 63 patients (52% males) with a median age at diagnosis of 64 years [Interquartile range (IQR)= 58-72] of which 38% (n=24) were Hispanic , 37% (n=23) Black, 14% (n=9) White, and 11% (n=7) other or unknown race. Smoking history, either former or active, was reported by 81% (n=51) of patients. Adenocarcinoma (84%, n=53) was the most frequent histological type followed by squamous cell carcinoma (10%, n=6) and large cell carcinoma (6%, n=4). PD-L1 expression was <1%, 1-49% and =>50% in 38% (n=24), 43% (n=27) and 14% (n=9) of patients, respectively. Anti-PD-1 and anti-PD-L1 therapy was administered to 81% and 19% of patients, respectively. Thirty-seven percent (n=23) of patients received concurrent chemotherapy. All patients had at least one dose of ICI with a median time of treatment of 4 months [IQR= 2-9]. Median TMB was 7 [IQR= 4-15]. No statistically significant difference was found in continuous TMB among different races or ethnicities (p>0.05). TMBlow and TMBhigh were found in 65% (n=40) and 35% (n=23) of patients, respectively. Median PFS was 4 months in patients with TMBlow compared to 8 months in patients with TMBhigh (p=0.121). Median OS was 12 months in patients with TMBlow compared to 17 months in patients with TMBhigh (p=0.187).
Conclusion
We observed a strong trend toward longer PFS and OS with TMBhigh compared to TMBlow in a uniquely diverse cohort of advanced NSCLC. Larger studies are warranted to understand the differences in molecular biomarkers across multiethnic groups and how these differences may predict the efficacy of ICI in advanced NSCLC.
