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Initial Patient Characteristics Associated With Ineligibility for Second-Line Therapy After Progression on First-Line
Hiroaki Kodama1, Haruyasu Murakami1, Nobuaki Mamesaya1
1Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
Background:
Osimertinib, an irreversible third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), improves survival in patients with EGFR-mutated non-small-cell lung cancer (NSCLC). However, a substantial proportion of patients do not proceed to subsequent therapy (ST). This study aimed to identify patient characteristics associated with ineligibility for post-osimertinib therapy.
Methods:
We retrospectively enrolled patients with EGFR-mutated NSCLC who received first-line osimertinib monotherapy between January 2016 and June 2023. Patients were categorized into a ST group and a non-subsequent therapy (NST) group. Baseline characteristics, treatment outcomes, and reasons for treatment discontinuation were documented.
Results:
Of 94 patients, 57 (60.6%) received ST, whereas 37 (39.4%) did not. The ST and NST groups significantly differed in age (p < 0.01) and prevalence of baseline central nervous system (CNS) metastases (24.1% vs. 54.1%, p < 0.01). The overall response rate to first-line osimertinib was similar (63.2% vs. 56.8%, p = 0.71), as was median progression-free survival (16.4 [95% confidence interval, CI: 12.4-21.4] vs. 16.1 months [95% CI: 9.8-19.3]; p = 0.24). The primary reason for not receiving subsequent treatment was deterioration in performance status, most often due to worsening pulmonary disease or CNS metastasis. In patients with baseline CNS metastasis, the main cause was also progression of CNS metastasis.
Conclusions:
Advanced age and baseline CNS metastasis are significant barriers to receiving second-line therapy after osimertinib monotherapy. Alternate first-line treatment strategies may be warranted for such patients.
Insights
Advanced age and central nervous system (CNS) metastases prevent many patients with EGFR-mutated non-small-cell lung cancer from receiving subsequent therapy after osimertinib treatment.
Area of Science:
- Oncology
- Medical Oncology
- Thoracic Oncology
Background:
- Osimertinib is a third-generation EGFR-TKI improving survival in EGFR-mutated NSCLC.
- A significant number of patients do not receive subsequent therapy (ST) after osimertinib.
- Identifying barriers to ST is crucial for optimizing patient care.
Purpose of the Study:
- To identify patient characteristics associated with ineligibility for post-osimertinib therapy.
- To analyze reasons for discontinuation of osimertinib and lack of subsequent treatment.
- To inform potential alternative first-line treatment strategies.
Main Methods:
- Retrospective enrollment of patients with EGFR-mutated NSCLC receiving first-line osimertinib.
- Categorization into ST and non-subsequent therapy (NST) groups.
- Documentation of baseline characteristics, treatment outcomes, and reasons for discontinuation.
Main Results:
- 39.4% of patients did not receive ST.
- Advanced age and baseline CNS metastases were significantly associated with lack of ST (p < 0.01).
- Worsening performance status, often due to CNS metastasis progression, was the primary reason for not receiving ST.
Conclusions:
- Advanced age and baseline CNS metastases are key barriers to ST after osimertinib.
- These factors may necessitate exploring alternative first-line treatment strategies.
- Further research into optimizing treatment sequencing for specific patient subgroups is warranted.
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