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Targeted therapy for localized non-small-cell lung cancer: a review
Nicolas Paleiron1, Olivier Bylicki2, Michel André1
1Chest Department, HIA Clermont Tonnerre, Brest.
Abstract:
Targeted therapies have markedly improved the management of patients with advanced non-small-cell lung cancer (NSCLC), but their efficacy in localized NSCLC is less well established. The aim of this review is to analyze trials of targeted therapies in localized NSCLC. In patients with wild-type EGFR, tyrosine kinase inhibitors have shown no efficacy in Phase III trials. Few data are available for EGFR-mutated localized NSCLC, as routine biological profiling is not recommended. Available studies are small, often retrospectives, and/or conducted in a single-center making it difficult to draw firm conclusions. Ongoing prospective Phase III trials are comparing adjuvant tyrosine kinase inhibitor administration versus adjuvant chemotherapy. By analogy with the indication of bevacizumab in advanced NSCLC, use of antiangiogenic agents in the perioperative setting is currently restricted to nonsquamous NSCLC. Several trials of adjuvant or neoadjuvant bevacizumab are planned or ongoing, but for the moment there is no evidence of efficacy. Data on perioperative use of biomarkers in early-stage NSCLC come mainly from small, retrospective, uncontrolled studies. Assessment of customized adjuvant or neoadjuvant therapy in localized NSCLC (with or without oncogenic driver mutations) is a major challenge.
Insights
Targeted therapies show limited efficacy in localized non-small-cell lung cancer (NSCLC). More research is needed to establish the role of tyrosine kinase inhibitors and antiangiogenic agents in early-stage NSCLC management.
Area of Science:
- Oncology
- Pulmonology
- Clinical Trials
Background:
- Targeted therapies have improved advanced non-small-cell lung cancer (NSCLC) treatment.
- Efficacy of targeted therapies in localized NSCLC remains less established.
- Limited data exist for EGFR-mutated localized NSCLC due to lack of routine profiling.
Purpose of the Study:
- To review and analyze clinical trials of targeted therapies in localized NSCLC.
- To assess the current evidence for tyrosine kinase inhibitors and antiangiogenic agents in early-stage NSCLC.
- To identify challenges in developing customized adjuvant or neoadjuvant therapies.
Main Methods:
- Systematic review of published trials and ongoing studies.
- Analysis of Phase III trials for tyrosine kinase inhibitors in wild-type EGFR NSCLC.
- Evaluation of data on antiangiogenic agents in the perioperative setting for NSCLC.
Main Results:
- Tyrosine kinase inhibitors demonstrated no efficacy in Phase III trials for wild-type EGFR localized NSCLC.
- Few conclusive data exist for EGFR-mutated localized NSCLC due to small, retrospective studies.
- Evidence for adjuvant or neoadjuvant bevacizumab in localized NSCLC is currently lacking.
Conclusions:
- Targeted therapies have a limited role in localized NSCLC currently.
- Further prospective trials are essential to determine the efficacy of adjuvant tyrosine kinase inhibitors and antiangiogenic agents.
- Developing customized perioperative therapies for localized NSCLC with or without driver mutations presents a significant challenge.
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