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Updated: May 28, 2025
Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
Investigating osimertinib plus chemotherapy in EGFR-mutated advanced non-small cell lung cancer
Alessia Spagnuolo1, Cesare Gridelli1
1Division of Medical Oncology, 'S. G. Moscati' Hospital, Avellino, Italy.
Introduction:
Worldwide, 15-40% of advanced-stage non-small cell lung cancers (NSCLCs) have an activating EGFR mutation, treatable with tyrosine-kinase inhibitors (TKIs) such as osimertinib, recommended as front-line therapy. Despite the efficacy of first-line osimertinib, most patients will experience disease progression. Therefore, combining it with chemotherapy has become an area of interest.
Areas Covered:
Osimertinib is a third-generation EGFR-TKI that has extended survival in NSCLC patients with EGFR mutation. However, resistance eventually leads to treatment failure. This has driven the advancement of strategies to overcome resistance to osimertinib. In this setting, the FLAURA2 trial yielded positive results by combining osimertinib with chemotherapy. Additionally, a range of other approaches, including the use of bispecific antibodies and antibody-drug conjugates alongside third-generation EGFR-TKIs or chemotherapy, support the development of novel therapeutic combinations, some of which have already been approved for EGFR-mutated advanced NSCLC.
Expert Opinion:
Next to osimertinib monotherapy, expanded upfront treatment options for patients with EGFR-mutated advanced NSCLC require patient selection considering disease extent, toxicity and tolerability, dosing schedule and what the patient can expect through shared decision-making. Further studies are needed to identify the patients who will benefit the most from combination therapies and to sequence the new drugs into the treatment algorithm.
Insights
First-line osimertinib is effective for EGFR-mutated non-small cell lung cancer (NSCLC), but resistance necessitates new strategies. Combining osimertinib with chemotherapy, as shown in the FLAURA2 trial, offers a promising approach to overcome treatment failure.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Activating EGFR mutations occur in 15-40% of advanced non-small cell lung cancers (NSCLCs).
- Osimertinib, a third-generation EGFR tyrosine-kinase inhibitor (TKI), is a recommended first-line therapy for EGFR-mutated NSCLC.
- Despite initial efficacy, most patients eventually develop resistance to osimertinib, leading to disease progression.
Purpose of the Study:
- To explore novel therapeutic combinations for EGFR-mutated advanced NSCLC.
- To evaluate strategies for overcoming osimertinib resistance.
- To discuss the implications of new treatment options on patient selection and sequencing.
Main Methods:
- Review of clinical trial data, including the FLAURA2 trial.
- Analysis of emerging therapeutic approaches like bispecific antibodies and antibody-drug conjugates.
- Consideration of factors for patient selection in upfront treatment decisions.
Main Results:
- The FLAURA2 trial demonstrated positive results combining osimertinib with chemotherapy.
- Several novel therapeutic combinations are being developed and some are approved for EGFR-mutated advanced NSCLC.
- Combination therapies represent a significant advancement in treating this patient population.
Conclusions:
- Combining osimertinib with chemotherapy is a promising strategy to overcome resistance in EGFR-mutated NSCLC.
- Further research is needed to identify optimal patient selection criteria and drug sequencing for combination therapies.
- Shared decision-making is crucial for integrating new treatment options into patient care.
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