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Patterns of initial and intracranial failure in metastatic EGFR-mutant non-small cell lung cancer treated with erlotinib.

ABSTRACT: Patients with metastatic EGFR-mutant (mEGFRmt) NSCLC have favorable survival when treated with erlotinib. We hypothesized that treatment failure in most patients is limited to initial sites of disease, in which case incorporating local therapy such as radiation might further delay progression. We therefore analyzed patterns and predictors of failure in a large cohort of such patients.We reviewed 189 patients treated with erlotinib for mEGFRmt NSCLC. We classified first pattern of failure as involving initial sites only (ISF), new sites only (NSF), or the combination (CSF), and used competing-risks regression to identify factors associated with ISF, progression and overall survival (OS). We also separately analyzed intracranial and intrathoracic failure.Of 171 patients who progressed, 103 (60.2%) had ISF, 30 (17.5%) had NSF, and 38 (22.2%) had CSF. Younger age and lack of initial CNS involvement independently correlated with ISF, with a trend for higher T and N stage. Higher T and N stage was also a significant predictor of progression. Factors predicting shorter OS were female gender, weight loss, initial intracranial involvement, and ?4 extracranial metastases. Intrathoracic progression was a component of first failure in 61%, and three-year cumulative incidence of brain metastasis was 30%.The main pattern of progression in mEGFRmt NSCLC on erlotinib is in the initial sites of disease. Younger patients and those without brain involvement are particularly likely to develop ISF. This suggests a role for incorporating local therapy into treatment of selected patients with mEGFRmt NSCLC.

SUBMITTER: Patel SH

PROVIDER: S-EPMC5477661 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Patterns of initial and intracranial failure in metastatic EGFR-mutant non-small cell lung cancer treated with erlotinib.

Patel Suchit H SH Rimner Andreas A Foster Amanda A Zhang Zhigang Z Woo Kaitlin M KM Yu Helena A HA Riely Gregory J GJ Wu Abraham J AJ

Lung cancer (Amsterdam, Netherlands) 20170324

<h4>Objectives</h4>Patients with metastatic EGFR-mutant (mEGFRmt) NSCLC have favorable survival when treated with erlotinib. We hypothesized that treatment failure in most patients is limited to initial sites of disease, in which case incorporating local therapy such as radiation might further delay progression. We therefore analyzed patterns and predictors of failure in a large cohort of such patients.<h4>Materials and methods</h4>We reviewed 189 patients treated with erlotinib for mEGFRmt NSCL ...[more]

PMID: 28625621

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Project description:BackgroundThe EGFR gene encodes a protein that stimulates molecular pathways that allow the growth and development of the tumor microenvironment. The current preferred tyrosine kinase inhibitor (TKI) for the first-line treatment of EGFRm metastatic non-small cell lung cancer (NSCLC) is osimertinib. However, the combination of angiogenesis inhibitors and TKI has produced discordant results. We aimed to assess the effects of the bevacizumab and erlotinib combination in EGFRm metastatic NSCLC.MethodsUsing eligibility criteria focused on patients with EGFRm metastatic NSCLC treated with bevacizumab and erlotinib, we searched databases including clinical trial randomized studies and reviews published until April 15, 2023 in Medline (PubMed), Scopus, and Embase. Eight clinical trials (1,052 patients) were selected from 1,343 articles for quantitative and qualitative assessment. The risk of bias was assessed using the Cochrane Risk of Bias tool. Data were synthesized through random-effects meta-analysis.ResultsThe bevacizumab and erlotinib combination significantly improved the progression-free survival (PFS) (log(HR) = 0.63; 95% CI: 0.54-0.73, p < 0.001) and overall response ratio (ORR) (RR = 0.79; 95% CI, 0.64-0.97, p = 0.03). However, it did not improve the overall survival (log(HR) = 0.93; 95% CI, 0.78-1.10, p = 0.38) and was associated with higher serious adverse events (SAEs) (OR = 3.48; 95% CI, 1.76-6.88, p = 0.005). A subgroup analysis suggested similar benefits in different mutation subtypes and brain metastasis condition. The evidence is limited by a moderate risk of bias across studies and heterogeneity in the reporting of SAEs.ConclusionsThe bevacizumab and erlotinib combination significantly improved PFS and ORR in EGFRm metastatic NSCLC but were also associated with higher-grade (≥3) adverse events. These results suggest that while the combination therapy may enhance progression-free survival and overall response, it does not improve the overall survival and is associated with higher toxicity. Thus, the treatment should be personalized based on individual patient comorbidities. Further prospective trials are needed to validate these results.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/#searchadvanced, identifier CDR 42022364692.

Dataset Information

Patterns of initial and intracranial failure in metastatic EGFR-mutant non-small cell lung cancer treated with erlotinib.

Publications

Patterns of initial and intracranial failure in metastatic EGFR-mutant non-small cell lung cancer treated with erlotinib.

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