Dataset Information

Optimizing Patient Outcomes Through Sequential EGFR TKI Treatment in Asian Patients With EGFR Mutation-Positive NSCLC.

ABSTRACT: Patients from Asia with non-small-cell lung cancer (NSCLC) often have mutations in the epidermal growth factor receptor (EGFR) gene. While an increasing number of EGFR tyrosine kinase inhibitors (TKIs) are now available for patients with EGFR mutation-positive NSCLC, most patients inevitably develop resistance to the treatment. Evidence from clinical studies suggests that treatment outcomes and resistance mechanisms vary depending on the choice of TKI therapy in the first-line setting. Hence, it is important to develop optimal treatment sequencing strategies that can provide maximum survival benefit for the patient. In this review we present clinical evidence in Asian patients with NSCLC for various EGFR TKIs, with the goal of supporting the optimization of treatment sequencing.

SUBMITTER: Liu R

PROVIDER: S-EPMC9234848 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Optimizing Patient Outcomes Through Sequential EGFR TKI Treatment in Asian Patients With EGFR Mutation-Positive NSCLC.

Liu Rong R Zhou Jianying J Ling Xia X

Clinical Medicine Insights. Oncology 20220624

Patients from Asia with non-small-cell lung cancer (NSCLC) often have mutations in the epidermal growth factor receptor (EGFR) gene. While an increasing number of EGFR tyrosine kinase inhibitors (TKIs) are now available for patients with EGFR mutation-positive NSCLC, most patients inevitably develop resistance to the treatment. Evidence from clinical studies suggests that treatment outcomes and resistance mechanisms vary depending on the choice of TKI therapy in the first-li ...[more]

PMID: 35770234

Similar Datasets

Project description:BackgroundIn individuals receiving treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), those exhibiting positive PD-L1 expression might experience reduced progression-free survival (PFS). However, the effects on overall survival (OS) and the determination of efficacious treatment approaches are still not well-defined.MethodsIn our retrospective study, we examined data from 193 NSCLC patients with advanced EGFR mutations who received first-line TKI treatments, treated at two centers of Shaw Hospital in Zhejiang, China. This analysis covered a period from 1 January 2016 to 30 April 2023.ResultsPatients with PD-L1 positivity exhibited a markedly shorter average PFS (9.5 months versus 17.8 months, P < 0.001) and OS (44.4 months versus 65.7 months, P = 0.016) relative to those without PD-L1 expression. This difference in both PFS and OS remained statistically significant even after adjusting for multiple factors (P < 0.001 for PFS and P = 0.028 for OS). In the PD-L1-positive cohort, introducing combination antiangiogenic significantly extended both PFS (from 9.1 to 25.7 months, P = 0.026) and OS (from 42 to 53.5 months, P = 0.03). Post-first-line TKI therapy, 39.3% of PD-L1-positive patients and 54.5% of PD-L1-negative patients developed the T790M mutation (P = 0.212), with no notable difference in PFS from second-line TKI treatments between the groups. Additionally, subsequent combination therapy with immunotherapy markedly prolonged OS in the PD-L1-positive group. However, for PD-L1-negative patients, neither combination antiangiogenic therapy nor later-line immunotherapy demonstrated significant benefits in PFS or OS.ConclusionFor PD-L1-positive patients, combined antiangiogenic treatments and immunotherapy can significantly improve survival outcomes. In contrast, PD-L1-negative patients show less benefit from these therapies, highlighting the greater efficacy of these treatments in PD-L1-positive individuals.

Project description:Few treatment options are available for brain metastases (BMs) in EGFR-mutant non-small cell lung cancer (NSCLC) that progress with prior EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy. This study aimed to evaluate the efficacy of immune checkpoint inhibitor (ICI) therapy in these patients. NSCLC patients with confirmed sensitive EGFR mutations and BMs were retrospectively reviewed. All patients experienced failure of EGFR-TKI therapy and were divided into two cohorts based on subsequent treatment. Cohort 1 included patients who received ICI therapy, while cohort 2 included patients treated with chemotherapy. Overall and intracranial objective response rates (ORRs) were used to evaluate the treatment response. Overall and intacranial progression-free survival (PFS) were calculated by Kaplan-Meier analysis and compared with the log-rank test. Univariate and multivariate Cox analyses were used to identify prognostic factors. A total of 53 patients treated with ICI therapy and 40 patients treated with chemotherapy were included in cohorts 1 and 2, respectively. In cohort 1, the overall ORR was 20.8%, with a median overall PFS of 4.2 months. The median intracranial PFS was 5.1 months. Of the 38 patients with measurable intracranial lesions, the intracranial ORR was 21.0%. Patients who received ICI combined with chemotherapy had the highest intracranial ORR of 37.5%. Compared to patients treated with chemotherapy in cohort 2, patients receiving ICI combined with chemotherapy had both longer intracranial PFS (6.4 vs. 5.1 months, p = 0.110) and overall PFS (6.2 vs. 4.6 months, p = 0.054), and these differences approached statistical significance. Univariate and multivariate Cox analyses demonstrated that high disease burden (p = 0.019), prior third-generation EGFR-TKI therapy (p = 0.019), and a poor lung immune prognostic index (LIPI) (p = 0.012) were independent negative predicators of overall PFS and that multiple BMs were negatively correlated with intracranial PFS among patients treated with ICI therapy. Our results suggested that ICI combined with chemotherapy had potent intracranial efficacy and may be a promising treatment candidate in EGFR-mutant NSCLC patients with BMs for whom prior EGFR-TKI therapy failed.

Project description:PurposeWe aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)-mutated patients with or without concomitant alterations.Materials and methodsThis multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non-small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR-tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint.ResultsThe overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment.ConclusionEGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.

Dataset Information

Optimizing Patient Outcomes Through Sequential EGFR TKI Treatment in Asian Patients With EGFR Mutation-Positive NSCLC.

Publications

Optimizing Patient Outcomes Through Sequential EGFR TKI Treatment in Asian Patients With <i>EGFR</i> Mutation-Positive NSCLC.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets