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 Choroidal metastases are the most common eye metastatic site. The prevalence of choroidal metastases in NSCLC patients has been reported to vary from 0.2 to 7% in historical series. Although previously reported, little is known about choroidal metastasis in Epidermal Growth Factor Receptor (EGFR)-mutant Non-small cell lung cancer (NSCLC). This study sought to describe the prevalence of choroidal metastases among patients with EGFR-mutated NSCLC and their characteristics, and to estimate their impact on prognosis. Methods We conducted a single-center retrospective study including all consecutive metastatic EGFR-mutant NSCLC patients, from Sept. 2015 to Oct. 2018. The EGFR-mutant NSCLC patients were identified via the Department of Genetics’ files. Patients who exhibited choroidal metastases were compared to patients without choroidal metastases. Kaplan-Meier analysis and log-rank test were conducted to assess median overall survival (OS) from diagnosis for the two groups. The study was approved by the IRB as CEPRO number #2020–010. 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.

Treatment of Choroidal Metastasis from Epidermal Growth Factor Mutant Non-Small Cell Lung Cancer with First-line Osimertinib Therapy

“…[ 5 ] Additionally, the presence of choroidal metastasis may occur in up to 8.4% of primary cases of EGFR + NSCLC. [ 6 ] The mean age of diagnosing uveal metastasis is 60 years and blurry or disturbed visual acuity is the most common presenting symptom. [ 1 , 7 , 8 ] In addition to blurry vision, the patient did report mild fatigue and weight loss.…”

Successful response to first-line treatment with osimertinib for choroidal metastasis from EGFR-mutated non-small-cell lung cancer

“… 6 It has been reported that the prevalence of choroidal metastases ranges from 0.2 to 7% in cases with NSCLC 7 , 8 with a recent case series showing the prevalence to be 8.4% in NSCLC cases with an EGFR mutation. 9 …”

“…Tyrosine kinase inhibitors (TKIs) targeting the EGFR pathway have become the gold standard of treatment for EGFR-mutated NSCLC. First and second generation EGFR-TKIs, such as gefitinib, erlotinib, or afatinib, have shown efficacy in treating choroidal metastasis, 9 , 10 , 11 but an EGFR T790 M resistance mutation can occur that limits the systemic efficacy of these treatments. 12 Osimertinib is an oral, third-generation, irreversible EGFR-TKI that selectively inhibits both EGFR-TKI–sensitizing and EGFR T790 M resistance mutations and has been shown to have improved overall survival over first generation EGFR-TKIs in previously untreated advanced stage NSCLC patients, as well as improved efficacy in the CNS.…”

“… 12 Osimertinib is an oral, third-generation, irreversible EGFR-TKI that selectively inhibits both EGFR-TKI–sensitizing and EGFR T790 M resistance mutations and has been shown to have improved overall survival over first generation EGFR-TKIs in previously untreated advanced stage NSCLC patients, as well as improved efficacy in the CNS. 13 While external beam radiation has historically been the gold standard for the treatment of choroidal metastases, osimertinib has been used with efficacy as a post-first-line and as a second/third-line treatment to successfully treat choroidal metastases, 9 , 14 prompting the suggestion to consider its use as a first-line therapy. 9 Here we describe a complete response of choroidal metastasis to osimertinib as the first-line treatment in a patient with EGFR-mutated lung adenocarcinoma.…”

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 (Bouchez et al 2020 ; Li et al 2016 ). The previous research has indicated that the ERBB receptor family is closely associated with cell proliferation and oncogenic events (Hyman et al 2018 ).…”