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Published on: June 26, 2019
Osimertinib for Chinese advanced non-small cell lung cancer patients harboring diverse EGFR exon 20 insertion
Guang-Jian Yang1, Jun Li2, Hai-Yan Xu3
1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17 Panjiayuan Street South, Chaoyang District, Beijing, 100021, China.
Objectives:
Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20 ins) mutations are generally associated with de novo resistance to first- or second-generation EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). However, the real efficacy of osimertinib for this subset remains elusive. We performed this study to investigate the real efficacy of osimertinib for Chinese advanced NSCLC patients harboring EGFR ex20 ins mutations.
Materials And Methods:
We retrospectively collected data of metastatic NSCLC patients with EGFR ex20 ins mutations who were treated with osimertinib 80 mg or 160 mg once daily in our center from June 2017 to May 2020. Progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were assessed.
Results:
A total of 62 cases with EGFR ex20 ins mutations were included, and the major insertion variant was D770_N771insSVD and V769_D770insASV (45.1 %). Concurrent TP53 mutation was most commonly observed (59.7 %). Four patients showed partial response, 29 cases with stable disease and 29 showed progressive disease as best response to osimertinib (ORR: 6.5 %, DCR: 53.2 %). The median PFS (mPFS) in total patients was 2.3 (95 %CI, 1.5-3.1) months. Patients harboring A763_Y764insFQEA/D770delinsGY variants showed numerically longer mPFS than those with other variants (4.2 vs. 2.2 months, P = 0.164). Patients who failed to osimertinib and occurred extracranial progression showed similar mPFS to those with intracranial progression (2.3 vs. 1.9 months, P = 0.142). Median PFS was not significantly different between patients who received osimertinib 80mg or 160mg once daily (2.5 vs. 1.3 months, P = 0.161), either with no significance when it used in fist-line setteing or bove (3.0 vs. 2.2 months, P = 0.639).
Conclusion:
The unique insertion variant A763_Y764insFQEA and D770delinsGY might better respond to osimertinib than other ex20 ins subtypes. Osimertinib either 80 mg or 160 mg once daily showed less activity in Chinese NSCLC patients harboring diverse EGFR ex20 ins mutations.
Insights
Osimertinib showed limited efficacy in Chinese non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion mutations. Certain variants like A763_Y764insFQEA may respond better, but overall outcomes were modest.
Area of Science:
- Oncology
- Medical Genetics
- Pharmacology
Background:
- Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations confer resistance to standard EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC).
- The efficacy of osimertinib, a third-generation EGFR inhibitor, in NSCLC patients with EGFR ex20ins mutations is not well-established.
- Understanding treatment outcomes for this specific mutation subset is crucial for optimizing NSCLC therapy.
Purpose of the Study:
- To evaluate the real-world efficacy of osimertinib in Chinese patients with advanced NSCLC harboring EGFR ex20ins mutations.
- To assess progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) with osimertinib treatment.
- To explore potential differences in response based on specific EGFR ex20ins variants and treatment dosages.
Main Methods:
- Retrospective analysis of 62 metastatic NSCLC patients with EGFR ex20ins mutations treated with osimertinib (80mg or 160mg daily).
- Data collected from June 2017 to May 2020.
- Key endpoints included PFS, ORR, and DCR.
Main Results:
- The most common variants were D770_N771insSVD and V769_D770insASV (45.1%). TP53 co-mutation was frequent (59.7%).
- Overall ORR was 6.5% and DCR was 53.2%, with a median PFS of 2.3 months.
- Patients with A763_Y764insFQEA/D770delinsGY variants showed numerically longer PFS (4.2 months) compared to others (2.2 months). No significant difference in PFS was observed between different osimertinib doses or first-line vs. later-line settings.
Conclusions:
- Osimertinib demonstrated limited overall activity in Chinese NSCLC patients with diverse EGFR ex20ins mutations.
- Specific variants, namely A763_Y764insFQEA and D770delinsGY, may exhibit a better response to osimertinib.
- Further research is warranted to identify optimal treatment strategies for NSCLC patients with EGFR ex20ins mutations.
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