Effectiveness of Immune Checkpoint Inhibitor Therapy on Bone Metastases in Non-Small-Cell Lung Cancer
Date
2023-07
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Abstract
Background: Bone metastases (BoMs) are prevalent in patients with metastatic non-small- cell lung cancer (NSCLC) and frequently result in intractable pain, pathologic fracture, and immobility. Patients who respond to immune checkpoint inhibitors (ICIs) demonstrate meaningful survival improvements, however, there are limited data detailing how BoMs respond. The primary aim of this study was to compare the response of BoMs against visceral lesions in patients treated with ICIs. The secondary aim was to evaluate the effect of BoMs on survival. Methods: A retrospective, multicenter cohort study was conducted in patients with NSCLC treated with ICI in Alberta, Canada from 2015 to 2020. The primary endpoint was the time to progression of bone versus visceral lesions measured with serial imaging studies. Visceral lesions were categorized as adrenal, brain, liver, lung, lymph node, or other intra- abdominal lesions. The secondary outcome was overall survival (OS) amongst patients with and without BoMs. Sub-group analysis was performed in patients with high PD-L1 expression (≥50%). Results: A total of 573 patients were included with a median age of 69.9 years (IQR: 60.6- 73.4) and 268 (46.8%) had high PD-L1 expression. All patients had visceral metastases and 243 patients (42.4%) had BoMs. Median OS for the entire cohort was 8.1 months (95%CI: 6.9-9.1) and median progression free survival (PFS) was 3.8 months (95%CI: 3.1-4.4). No difference was found between the time to progression of bone, liver, and intra-abdominal lesions (p=0.20, p=0.76), but BoMs demonstrated faster progression than the other sites of disease. Subgroup analysis of patients with high PD-L1 expression (≥50%) demonstrated no significant difference in the time to progression between extra-thoracic sites of disease, including BoMs. The presence of BoMs was found to be an independent prognostic factor for OS (HR 1.26, 95%CI: 1.05-1.53, p=0.01) but this was not significant in the high PD-L1 expression subgroup (HR: 1.24, 95%CI: 0.92-1.68, p=0.16). Conclusion: Bone, liver, and intra-abdominal lesions demonstrated a significantly shorter time to progression than other visceral lesions, and patients with BoMs had inferior clinical outcomes. PD-L1 status was identified as an important biomarker predicting response, as patients with high PD-L1 expression demonstrated equivalent responses to ICI amongst extra-thoracic sites of disease.
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Keywords
Immunotherapy, Lung Cancer, Metastatic Bone Disease
Citation
Abbott, A. G. (2023). Effectiveness of immune checkpoint inhibitor therapy on bone metastases in non-small-cell lung cancer (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.