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Efficacy of dacomitinib in patients with non-small cell lung cancer carrying complex EGFR mutations: a real-world
Hong-Shuai Li1, Jun-Ling Li1, Xiang Yan2
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, Beijing, China.
Background:
Dacomitinib is a first-line treatment for patients with non-small cell lung cancer (NSCLC) harboring common epidermal growth factor receptor (EGFR) mutations; however, clinical evidence of its activity on NSCLC with complex EGFR mutations is limited.
Methods:
Patients harboring complex (common mutations co-existing with uncommon mutations), or common (comparison cohort) EGFR mutations, who were treated with dacomitinib, were retrospectively evaluated in the Chinese National Cancer Center and the China PLA hospital between August 2019 and August 2021.
Results:
In total, 72 patients with NSCLC harboring complex (C+U group, n=18) or common (C group, n=54) EGFR mutations and being treated with dacomitinib were enrolled. In the C+U group, 16 cases (88.9%) harbored L858R mutations co-existing with uncommon mutations located from exon 18 to exon 25 of EGFR (mostly E709X), and two cases harbored exon 19 deletion co-existing with G724S or K754E. Among the 15 evaluable patients, the objective response rate (ORR) was 40% (6/15), and the disease control rate (DCR) was 73.3% (11/15). The median progression-free survival (PFS) was 7.5 months [95% confidence interval (CI), 4.4-10.6 months]. Except for the application line of dacomitinib (P=0.039), no significant statistical differences were found in other characteristics and adverse events between the two groups. The Kaplan-Meier method revealed no significant differences in PFS (P=0.889) and overall survival (OS) (P=0.703). However, the stratified analysis found worse PFS in the C+U group than that observed in the C group when receiving 1st and ≥3rd line dacomitinib treatment, while its OS was worse than that of group C when receiving ≥3rd line treatment. Furthermore, in a multivariate analysis, complex mutation status was an independent prognostic factor for OS (P=0.038) in the entire cohort.
Conclusions:
This study indicated a worse response and prognosis of patients with NSCLC harboring complex EGFR mutations than those harboring common EGFR mutations when treated with dacomitinib. Further studies and data are needed to confirm this conclusion.
Insights
Dacomitinib shows limited efficacy in non-small cell lung cancer (NSCLC) with complex EGFR mutations. Patients with complex mutations experienced worse outcomes compared to those with common mutations.
Area of Science:
- Oncology
- Genetics
Background:
- Dacomitinib is a first-line treatment for non-small cell lung cancer (NSCLC) with common epidermal growth factor receptor (EGFR) mutations.
- Limited clinical evidence exists for dacomitinib's efficacy in NSCLC with complex EGFR mutations.
Purpose of the Study:
- To evaluate the clinical activity and prognosis of dacomitinib in NSCLC patients with complex versus common EGFR mutations.
- To compare treatment response and survival outcomes between these two patient groups.
Main Methods:
- Retrospective evaluation of 72 NSCLC patients treated with dacomitinib.
- Patients were categorized into complex (common and uncommon mutations) and common EGFR mutation groups.
- Kaplan-Meier and multivariate analyses were used to assess progression-free survival (PFS) and overall survival (OS).
Main Results:
- Complex EGFR mutations (n=18) showed an objective response rate (ORR) of 40% and disease control rate (DCR) of 73.3%.
- No significant difference in median PFS or OS between groups overall.
- Stratified analysis revealed worse PFS and OS in the complex mutation group, particularly in later treatment lines. Complex mutation status was an independent prognostic factor for OS.
Conclusions:
- NSCLC patients with complex EGFR mutations exhibit poorer response and prognosis with dacomitinib compared to those with common mutations.
- Further research is necessary to validate these findings and explore alternative treatment strategies.
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