Date of Award

January 2024

Document Type

Open Access Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Shiyi Wang

Second Advisor

Szuchun Yang

Abstract

Introduction: Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a leading cause of cancer-related mortality worldwide. While immunotherapy has revolutionized the treatment landscape for advanced NSCLC, optimal first-line therapy for patients with programmed death-ligand 1 (PD-L1) expression levels between 1-49% remains uncertain.

Objective: To investigate the comparative effectiveness of different first-line treatment options for advanced NSCLC patients with PD-L1 expression levels between 1-49%.

Methods: We conducted a retrospective analysis using patient data from the Flatiron Health database. Our patient sample includes adult patients diagnosed with advanced NSCLC between 2016 and 2021, with PD-L1 expression levels ranging from 1-49%. Treatment modalities assessed included immunotherapy (IO), IO combined with platinum doublet chemotherapy, and platinum doublet chemotherapy alone. Progression-free survival (PFS) and overall survival (OS) were evaluated using multi-variate cox-proportional hazard model to adjust for potential confounders.

Results: Among 3,907 eligible patients, those receiving IO + platinum doublet and platinum doublet alone showed significantly higher PFS compared to IO alone (HR 0.84, 95% CI: 0.74-0.95, p=0.005; HR 0.86, 95% CI: 0.76-0.98, p=0.02, respectively). After multivariable Cox-proportional hazard regression adjusting for potential confounders, IO alone was still associated with increased risk of progression. However, in terms of OS probabilities, IO and IO + platinum doublet OS probabilities were similar (HR 1.06, 95% CI: 0.95-1.18, p=0.3) while platinum doublet therapy showed significantly superior efficacy than IO (HR 0.89, 95% CI: 0.80-1.00, p=0.044).

Conclusion: Adding platinum-based chemotherapy to immunotherapy or using chemotherapy alone may delay disease progression in advanced NSCLC patients with PD-L1 1-49%. However, when considering overall survival, only platinum doublet therapy exhibited an advantage over IO alone. Further research is warranted to validate these findings and guide treatment decisions for this patient population.

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This is an Open Access Thesis.

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