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Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
Published on: May 20, 2020
Dynamic changes in quality of life after three first-line therapies for EGFR mutation-positive advanced
Szu-Chun Yang1, Chien-Chung Lin2, Wu-Wei Lai3
1Department of Internal Medicine, National Cheng Kung University Hospital and Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Background:
Three different tyrosine kinase inhibitors have been approved as first-line therapies for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer with similar overall survival. This study determined dynamic changes in quality of life (QoL) for patients using these therapies after controlling for potential confounders.
Methods:
From 2011 to 2016, we prospectively assessed the utility values and QoL scores of patients using the EuroQol five-dimension and World Health Organization Quality-of-Life - Brief questionnaires. QoL functions after initiation of treatment were estimated using a kernel-smoothing method. Dynamic changes in major determinants were repeatedly assessed for constructing mixed models.
Results:
A total of 344 patients were enrolled, with 934 repeated assessments. After controlling for performance status, disease progression, EGFR mutation subtype and other confounders, the mixed models showed significantly lower QoL scores for afatinib versus gefitinib in the physical, psychological and social domains, and 10 facets. The differences seemed to appear 10 months after initiation of treatment. In contrast, there was no significant difference between erlotinib and gefitinib in the scores of all domains and facets.
Conclusion:
QoL in patients receiving afatinib seemed to be lower than in those receiving gefitinib. Since the sample sizes in this study were relatively small, more studies are warranted to corroborate these results.
Insights
Quality of life (QoL) was assessed in patients with advanced non-small-cell lung cancer receiving tyrosine kinase inhibitors. Afatinib showed lower QoL scores compared to gefitinib, with differences emerging around 10 months post-treatment.
Area of Science:
- Oncology
- Pharmacology
- Health Outcomes Research
Background:
- First-line therapies for EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC) include three tyrosine kinase inhibitors with similar overall survival.
- Quality of life (QoL) is a critical factor in treatment selection for NSCLC patients.
Purpose of the Study:
- To dynamically assess and compare the quality of life (QoL) among patients with advanced non-small-cell lung cancer (NSCLC) treated with three different first-line tyrosine kinase inhibitors.
- To identify potential differences in QoL domains and facets over time, controlling for key patient and disease characteristics.
Main Methods:
- Prospective assessment of utility values and QoL using EuroQol five-dimension and WHOQOL-BREF questionnaires from 2011-2016.
- Kernel-smoothing methods to estimate QoL functions and mixed models to analyze dynamic changes in QoL determinants.
- Control for confounders including performance status, disease progression, and EGFR mutation subtype.
Main Results:
- Analysis of 344 patients with 934 repeated assessments revealed significantly lower QoL scores for afatinib compared to gefitinib across physical, psychological, and social domains.
- These QoL differences favoring gefitinib over afatinib appeared approximately 10 months after treatment initiation.
- No significant QoL differences were observed between erlotinib and gefitinib in any domain or facet.
Conclusions:
- Patients receiving afatinib experienced diminished quality of life compared to those treated with gefitinib.
- The findings suggest potential differences in long-term QoL impact among first-line EGFR inhibitors for NSCLC.
- Further research with larger sample sizes is recommended to validate these QoL findings.
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