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Site-Specific Response and Resistance Patterns in Patients with Advanced Non-Small-Cell Lung Cancer Treated with
Lauren Julia Brown1,2,3,4, Julie Ahn2,5, Bo Gao1,2,3
1Department of Medical Oncology, Westmead Hospital, Sydney, NSW 2145, Australia.
Abstract:
Patients with advanced NSCLC have heterogenous responses to immune checkpoint inhibitors (ICIs) with or without chemotherapy. In NSCLC, the impact of the distribution of metastatic sites and the response to systemic therapy combinations remain poorly understood. In a retrospective cohort study of patients with unresectable stage III/IV NSCLC who received first-line systemic therapy, we sought to assess the association between the site of metastases with patterns of response and progression. Data regarding demographics, tumour characteristics (including site, size, and volume of metastases), treatment, and outcomes were examined at two cancer care centres. The endpoints included organ site-specific response rate, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Two-hundred and eighty-five patients were included in the analysis. In a multivariate analysis, patients with bone metastases had a reduced ORR, PFS, and OS. Primary resistance was also more likely in patients with bone metastases. Patients with bone or liver metastases had a shorter OS when receiving ICIs with or without chemotherapy, but not with chemotherapy alone, suggesting an immunological basis for therapeutic resistance. A directed assessment of the tumour microenvironment in these locations and a deeper understanding of the drivers of organ-specific resistance to immunotherapy are critical to optimise novel combination therapies and sequencing in these patients.
Insights
Bone metastases in advanced non-small cell lung cancer (NSCLC) are linked to poorer responses and survival with immune checkpoint inhibitors (ICIs). Understanding organ-specific resistance is key for optimizing NSCLC treatment strategies.
Area of Science:
- Oncology
- Immunotherapy
- Translational Research
Background:
- Advanced non-small cell lung cancer (NSCLC) patients show varied responses to immune checkpoint inhibitors (ICIs) and chemotherapy.
- The influence of metastatic site distribution on treatment outcomes in NSCLC is not well understood.
Purpose of the Study:
- To investigate the association between the location of metastases and treatment response and progression in patients with unresectable stage III/IV NSCLC.
- To evaluate how metastatic site impacts outcomes with first-line systemic therapies, including ICIs.
Main Methods:
- Retrospective cohort study of 285 patients with unresectable stage III/IV NSCLC receiving first-line systemic therapy.
- Analysis of demographics, tumor characteristics (metastases site, size, volume), treatment, and outcomes, including organ site-specific response rate, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).
Main Results:
- Patients with bone metastases experienced reduced ORR, PFS, and OS, with higher rates of primary resistance.
- Bone or liver metastases were associated with shorter OS when treated with ICIs (with or without chemotherapy), but not chemotherapy alone.
- Findings suggest an immunological basis for therapeutic resistance in specific metastatic sites.
Conclusions:
- Metastatic site, particularly bone, significantly impacts treatment efficacy and survival in advanced NSCLC patients receiving ICIs.
- Organ-specific resistance mechanisms in NSCLC require further investigation to optimize immunotherapy combinations and treatment sequencing.
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