Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer and Choroidal Metastases: Long-Term Outcome and Response to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Abstract

Background: Although previously reported, little is known about choroidal metastasis in EGFR-mutant NSCLC. Methods: In this single-center retrospective cohort including 83 consecutive metastatic EGFR-mutant NSCLC patients, from Sept. 2015 to Oct. 2018, six exhibited symptomatic choroidal metastases. All brain MRI scans performed in the EGFR-mutant patients were reviewed, with one case of asymptomatic choroidal metastasis identified. Kaplan-Meier analysis and log-rank test were conducted to assess median overall survival (OS) from diagnosis for the two groups, with or without choroidal metastases.Results: Prevalence of choroidal metastases in EGFR-mutated NSCLCs was 8.4% (7/83). Five were women, and four current or former smokers. Molecular analysis showed three tumors with exon 19 deletion, three with L858R mutation, and one with complex exon 21 mutation. The choroidal metastases were symptomatic in six/seven patients. Visual disturbances decreased in all but one symptomatic cases upon EGFR TKI, and the choroidal response was maintained over time. Median follow-up was 42.2 mo (95%CI [37.2 - 47.1]). Median OS in the choroidal metastasis group was 23.4 mo (95%CI [0.1 - 51.4]) versus 27.9 mo (95%CI [16.9 - 38.9]) in the non-choroidal metastasis group (p=0.32). In the choroidal metastasis group, 2-year and 5-year OS were 47.6% and 0%, respectively, versus 55.8% and 26.3% in the non-choroidal metastasis subset.Conclusions: Choroidal metastases in NSCLC EGFR-mutant patients are rare but should be systematically suspected in case of visual disturbance. TKIs are efficient for treating visual symptoms. Whether choroidal metastases confer a worse prognosis remains unclear owing to the third-generation EGFR TKI osimertinib first-line registration.

Effect of the First-Line Therapy with Osimertinib for a Metastatic Choroidal Tumor in Advanced-Stage Lung Cancer: A Case Report

“…They reported complete resolution within 3 months and maintenance for 17 months. In many cases, osimertinib has been associated with a reduction in choroidal lesions and improvement in symptoms such as visual disturbances, brain metastases, and metastatic disease [4,[7][8][9]. The reported side effects were within the control limits [8].…”

“…The case reports on the efficacy of osimertinib in metastatic choroidal tumors of primary NSCLC are summarized in Table 1. Previously, osimertinib was often reported as a second-line therapy [4,7,8,11], but since the FLAURA trial, osimertinib has been used as a first-line therapy. However, few reports have demonstrated the efficacy of osimertinib as a first-line therapy for metastatic choroidal tumors [9,10].…”

“…Choroidal metastases occur in 0.2-7% of patients with NSCLC. A recent report showed a prevalence of 8.4% of choroidal metastases in patients with EGFR-mutant NSCLC [4].…”

“…Systemic administration of EGFR-TKIs has been reported to be effective for choroidal metastases in EGFR-mutant NSCLC, and the efficacy of osimertinib has recently been reported [4,[7][8][9][10][11]. An attempt to use osimertinib as the first-line drug for choroidal metastasis in EGFR-mutant NSCLC is also under investigation.…”

The Role of ERBB4 Mutations in the Prognosis of Advanced Non-small Cell Lung Cancer Treated With Immune Checkpoint Inhibitors

“…Tyrosine kinase receptors of the ERBB family include four members: HER-1/ERBB1/EGFR, HER-2/ ERBB2, HER-3/ ERBB3, and HER-4/ ERBB4 [18,19]. The former researches indicated that the ERBB receptor family is closely associated with cell proliferation and oncogenic events [20].…”