Immune Checkpoint Inhibitor-Based Therapy as the First-Line Treatment for Advanced Non-Small Cell Lung Cancer:
Xingxiang Pu1, Yu Zhou2, Jingyi Wang3
1Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, China.
Abstract:
The selection of initial systemic treatment for advanced non-small cell lung cancer (NSCLC) depends on histological subtypes, oncogenic driver identification through genomic profiling, and programmed death-ligand 1 (PD-L1) expression quantification. The choice of first-line treatment is crucial as patients with advanced NSCLC may not have the opportunity to receive second- or later-line therapies due to the rapid progression of the disease. Current guidelines recommend pretreatment PD-L1 expression quantification evaluation prior to initiating systemic therapy in advanced NSCLC. Except for histology, PD-L1 expression, and absence of actionable driver mutations, single-agent immune checkpoint inhibitors (ICIs) are foundational first-line interventions. ICIs combined with chemotherapy or other ICIs have shown improved survival outcomes compared to ICI monotherapy. However, choosing the best option can be challenging due to limited head-to-head comparisons. Treatment decisions are often influenced by drug availability, reimbursement coverage, and patient's economic conditions. Despite the development of new ICI therapies, overall survival data seem to have plateaued, highlighting the need for sustained investigations and extensive clinical validation studies to develop novel therapies, optimize ICI combinations, and monitor adverse effects. Collaboration among data scientists, clinicians, biologists, and policymakers is essential to establish biomarkers that enhance patient selection and overall survival in NSCLC.
Insights
Choosing first-line treatment for advanced non-small cell lung cancer (NSCLC) involves PD-L1 testing and genomic profiling. Optimizing immune checkpoint inhibitor (ICI) combinations is key, but survival gains are plateauing, necessitating new biomarkers and therapies.
Area of Science:
- Oncology
- Immunotherapy
- Genomics
Background:
- First-line treatment selection for advanced non-small cell lung cancer (NSCLC) is critical due to rapid disease progression.
- Treatment decisions depend on histology, genomic profiling for driver mutations, and PD-L1 expression.
- Current guidelines emphasize PD-L1 evaluation before initiating systemic therapy.
Purpose of the Study:
- To review current strategies for selecting first-line systemic treatment in advanced NSCLC.
- To discuss the role of immune checkpoint inhibitors (ICIs) and combination therapies.
- To highlight challenges and future directions in optimizing NSCLC treatment.
Main Methods:
- Review of current guidelines and clinical practice for advanced NSCLC.
- Analysis of the role of PD-L1 expression and genomic profiling.
- Examination of ICI monotherapy versus combination strategies (chemotherapy or other ICIs).
Main Results:
- Single-agent ICIs are foundational, but combinations with chemotherapy or other ICIs show improved survival.
- Limited head-to-head comparisons complicate optimal choice selection.
- Treatment decisions are influenced by practical factors like drug availability and cost.
Conclusions:
- Despite advances in ICIs, overall survival in advanced NSCLC appears to be plateauing.
- Further research is needed to develop novel therapies and optimize ICI combinations.
- Biomarker discovery and collaborative efforts are essential for improving patient selection and survival outcomes.
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