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Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Parameters for individualizing systemic therapy in non-small cell lung cancer
Shirish M Gadgeel1, Michele L Cote, Ann G Schwartz
1Department of Oncology, Wayne State University, MI 48201, USA.
Abstract:
Rational drug design based on molecular targets is starting to revolutionize cancer care. To maximize its potential for patients, a concomitant leveraging of molecular knowledge for selection of patients to future and current therapeutic options is paramount. The terms "individualized", "personalized", or "precision therapy" are currently used to describe these efforts. Here, we summarize current knowledge for selection of systemic targeted and cytotoxic therapy for patients with non-small-cell lung cancer. Based on this knowledge, we present a potential decision algorithm to best select patients for currently available therapies, which include the treatment options single-agent erlotinib or gefitinib, the ALK inhibitor crizotinib, double agent gemcitabine and platinum, double agent platinum and pemetrexed, and as a default option a taxane combined with a non-platinum drug, for instance a vinca alkaloid. The addition of bevacizumab to double-agent chemotherapy is also discussed. Currently available data on predictive biomarkers are largely based on subgroup or companion biomarker analyses of patient cohorts or clinical trials. Current and emerging markers must be incorporated prospectively into the design of clinical trials that test novel and established agents to better understand their clinical utility and to refine selection parameters and marker interactions. Future development will lead to increasing complexity in clinical decision making with substantial anticipated benefits to patients including increased therapeutic efficacy, reduced toxicity, and better quality of life.
Insights
Precision therapy in non-small-cell lung cancer (NSCLC) uses molecular knowledge to guide treatment selection. This approach optimizes patient outcomes by matching individuals to targeted or cytotoxic therapies, improving efficacy and quality of life.
Area of Science:
- Oncology
- Pharmacogenomics
- Translational Medicine
Background:
- Molecularly targeted drugs are transforming cancer care.
- Personalized medicine, including individualized, precision therapy, requires leveraging molecular knowledge for patient selection.
- Non-small-cell lung cancer (NSCLC) treatment selection is complex.
Purpose of the Study:
- To summarize current knowledge on selecting systemic targeted and cytotoxic therapies for NSCLC patients.
- To present a decision algorithm for optimizing patient selection for available NSCLC therapies.
- To discuss the role of predictive biomarkers and future research directions.
Main Methods:
- Review of current knowledge on patient selection for NSCLC therapies.
- Development of a potential decision algorithm for therapy selection.
- Discussion of available targeted agents (erlotinib, gefitinib, crizotinib) and cytotoxic regimens (gemcitabine/platinum, platinum/pemetrexed, taxane/non-platinum, bevacizumab combinations).
Main Results:
- Current NSCLC therapies include single-agent targeted drugs, combination chemotherapy, and bevacizumab.
- Predictive biomarker data often comes from subgroup analyses; prospective incorporation into trials is needed.
- A decision algorithm can aid in selecting appropriate therapies based on molecular profiles.
Conclusions:
- Personalized medicine in NSCLC aims to maximize therapeutic potential through molecularly guided patient selection.
- Prospective integration of biomarkers into clinical trials is crucial for refining selection parameters and understanding marker interactions.
- Future advancements will enhance clinical decision-making, leading to increased efficacy, reduced toxicity, and improved patient quality of life.
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