Dataset Information

Optimal sequence of LT for symptomatic BM in EGFR-mutant NSCLC: a comparative study of first-line EGFR-TKIs with/without upfront LT.

ABSTRACT:

Background

The third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can penetrate blood-brain barrier and are effective for brain metastases (BMs). There is no consensus on the optimal sequence of local therapy (LT) and EGFR-TKIs for symptomatic BM patients because patients suffering neurological symptoms were not enrolled in most clinical trials.

Methods

Non-small cell lung cancer (NSCLC) patients with EGFR mutation (EGFRm) and symptomatic BM receiving first-line osimertinib and aumolertinib from two medical centers were collected. All participants were allocated into the third-generation EGFR-TKIs (TKIs) group and the upfront LT (uLT) plus third-generation EGFR-TKIs (TKIs + uLT) group. Demographic data, survival outcomes, treatment failure patterns, and adverse events were evaluated between the two groups. We also conducted subgroup analyses to explore the impact of BM number on survival outcomes.

Results

86 patients were enrolled, 44 in the TKIs group and 42 in the TKIs + uLT group. There were no significant differences in the short-term response between the groups. TKIs + uLT was associated with significantly longer overall survival (OS) (43 vs. 28 months; hazard ratio [HR], 0.36, 95% confidence interval [CI], 0.17-0.77; p = .011). No differences in progression-free survival (PFS), intracranial PFS (iPFS), failure patterns, or safety were observed. In subgroup analyses of oligo-BM patients, TKIs + uLT could prolong OS (43 vs. 31 months; HR 0.22; 95% CI 0.05-0.92; p = .015).

Conclusions

EGFRm NSCLC patients with symptomatic BM might benefit from uLT, particularly oligo-BM patients. However, larger prospective cohort studies should be carried out to confirm the responses of the TKIs + uLT scheme.

SUBMITTER: Niu L

PROVIDER: S-EPMC10874906 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Optimal sequence of LT for symptomatic BM in EGFR-mutant NSCLC: a comparative study of first-line EGFR-TKIs with/without upfront LT.

Niu Lishui L Wu Honghua H Gao Ruihuan R Chen Liu L Wang Jiangtao J Duan Hexin H Long Yujiao Y Xie Yi Y Zhou Qin Q Zhou Rongrong R

Journal of cancer research and clinical oncology 20240219 2

<h4>Background</h4>The third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can penetrate blood-brain barrier and are effective for brain metastases (BMs). There is no consensus on the optimal sequence of local therapy (LT) and EGFR-TKIs for symptomatic BM patients because patients suffering neurological symptoms were not enrolled in most clinical trials.<h4>Methods</h4>Non-small cell lung cancer (NSCLC) patients with EGFR mutation (EGFRm) and symptomatic BM r ...[more]

PMID: 38369644

Similar Datasets

Project description:BackgroundEpidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the established first-line treatment for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, but survival advantages in advanced-stage cases remain modest and show interpatient variability. This study seeks to delineate real-world survival outcomes in stage IV EGFR-mutant NSCLC patients undergoing treatment with EGFR-TKIs and to identify independent prognostic factors impacting overall survival (OS). The findings are expected to be a reference for clinicians in managing advanced lung cancer patients.MethodsClinical characteristics from advanced EGFR-mutant NSCLC patients who received EGFR-TKIs were retrospectively analyzed to investigate the association between clinical factors and overall survival.ResultsThe median OS was 40.60 months (95% confidence interval: 34.72-46.48 months), with expected 1-, 3-, and 5-year OS of 87.2%, 57.8%, and 34.0%, respectively. Patients exhibiting specific characteristics, such as being under 60 years old, having stage IVA disease, adenocarcinoma histology, no liver or brain metastases, negative for neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), cytokeratin fragment 19 (CYFRA 21 - 1), progastrin-releasing peptide (ProGRP), and those who received chemotherapy and radiotherapy exhibited significantly longer survival times compared to patients with the opposite characteristics (being 60 years or older, having stage IVB or IVC disease, non-adenocarcinoma histology, presence of liver or brain metastases, positive for CEA, NSE, ProGRP, CYFRA 21 - 1, and not receiving chemotherapy or radiotherapy) (P < 0.05). Cox univariate and multivariate analyses identified pathological type, liver metastasis, brain metastasis, NSE, CYFRA 21 - 1, EGFR-TKIs type, radiotherapy, and chemotherapy as independent prognostic factors for patients with stage IV NSCLC treated with EGFR-TKIs.ConclusionsPathological type, liver metastasis, brain metastasis, NSE, and CYFRA 21 - 1 were identified as independent risk factors for stage IV NSCLC patients treated with EGFR-TKIs, while chemotherapy and radiotherapy were determined to be independent protective factors. Taking icotinib or gefitinib, as opposed to osimertinib, was an independent risk factor for advanced NSCLC patients.

Project description:The impact of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy as first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) remains controversial. Therefore, randomized trials that compared this combined regimen with chemotherapy or EGFR-TKIs monotherapy were included for this meta-analysis. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of the combined regimen in the entire unselected population and selected patients by EGFR-mutation status and smoking history were calculated. Eight trials eventually entered into this meta-analysis, including 4585 patients. Overall, the combined regimen significantly delayed disease progression (HR?=?0.81, 95% CI 0.69-0.95, P?=?0.01); subgroup analysis showed significantly higher progression free survival advantages in Asian patients (P<0.001), with sequential combination of TKIs and chemotherapy (P?=?0.02). In selected patients by EGFR-mutation, both mutation positive (HR?=?0.48, 95% CI 0.28-0.83, P?=?0.009) and negative (HR?=?0.84, 95% CI 0.72-0.98, P?=?0.02) patients gained progression free survival benefit from the combined regimen, albeit the magnitude of benefit was marginally larger in mutation positive patients (P?=?0.05). In selected patients by smoking history, never/light smokers achieved a great progression free survival benefit from the combined regimen (HR?=?0.51, 95% CI 0.35-0.74, P?=?0.0004). Unfortunately, the combined regimen had no significant impact on overall survival, irrespective of ethnicity, dose schedules or EGFR-mutation status. Severe anorexia (RR?=?2.01, 95% CI 1.11-3.63; P?=?0.02) and diarrhea (RR?=?2.70, 95% CI 1.94-3.76; P<0.001) were more frequent in the combined regimen arm. This strategy of combining EGFR-TKIs and chemotherapy deserved to be considered in the future, although it is not approved for advanced NSCLC at the moment.

Project description:BackgroundIn previous studies, the predictive role of BIM deletion polymorphism with respect to responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has been controversial. The potential reasons for these inconsistent findings were unknown.MethodsData from CTONG0901 clinical trial and medical records of Guangdong Lung Cancer Institute (GLCI) were retrospectively pooled. A total of 194 and 141 EGFR-mutant non-small cell lung cancer (NSCLC) patients treated with first- and second-generation EGFR-TKIs were examined in the CTONG0901 and GLCI cohorts, respectively. Sixty-eight patients were treated with third-generation EGFR-TKIs in the GLCI cohort. The BIM gene status was examined by next-generation sequencing.ResultsThe frequency of BIM deletion polymorphism was 11.3% and 17.0% in CTONG0901 and GLCI cohorts, respectively. For first- and second-generation EGFR-TKIs in CTONG0901 cohort, objective response (ORR) was 54.5% in BIM deletion group versus 56.4% in wild-type BIM group (P = .87); disease control rate (DCR) was 90.9% versus 88.4% (P = 1.00); progression-free survival (PFS) was 10.5 versus 11.2 months (P = .59); and overall survival (OS) was 20.5 versus 20.5 months (P = .73). In GLCI cohort, ORR was 54.2% versus 60.7% (P = .55); DCR was 91.7% versus 96.6% (P = .27); PFS was 10.1 versus 11.6 months (P = .63); and OS was 58.5 versus 45.0 months (P = .93). For third-generation EGFR-TKIs, ORR was 18.2% versus 63.2% (P = .02); DCR was 81.8% versus 96.5%, (P = .12); PFS was 5.8 versus 9.0 months (P = .13); and OS was 30.0 versus 24.8 months (P = .85). Cox regression analysis showed that concomitant genetic alterations could adversely affect the response to EGFR-TKIs, but not BIM deletion.ConclusionsThe presence of BIM deletion showed no relation to an impaired response to first-, second-, and third-generation EGFR-TKIs in NSCLC patients. The factors influencing the response of EGFR-TKIs were concomitant genetic alterations, but not BIM deletion.

Dataset Information

Optimal sequence of LT for symptomatic BM in EGFR-mutant NSCLC: a comparative study of first-line EGFR-TKIs with/without upfront LT.

Background

Methods

Results

Conclusions

Publications

Optimal sequence of LT for symptomatic BM in EGFR-mutant NSCLC: a comparative study of first-line EGFR-TKIs with/without upfront LT.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets