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Immunotherapy combined with epidermal growth factor receptor-tyrosine kinase inhibitors in non-small-cell lung cancer treatment.

ABSTRACT: In recent years, targeted therapy and immunotherapy have played important roles in the treatment of patients with non-small-cell lung cancer (NSCLC). Drugs that target epidermal growth factor receptor (EGFR) mutations (eg, gefitinib, erlotinib, icotinib, and osimertinib) are among the most commonly used targeted therapies. Afatinib is an irreversible second-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI), and the LUX-Lung 3 trial demonstrated the superiority of afatinib to cisplatin and pemetrexed in the frontline treatment of treatment-naïve patients with advanced EGFR mutation adenocarcinoma of the lung. Although these drugs show significant therapeutic efficacy, most patients invariably experience disease progression resulting in death. Immunotherapy targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) has now been approved for the first-line treatment of patients with advanced NSCLC. These can produce sustained clinical responses by reversing negative regulators of T-cell function; however, immunotherapy response rates remain low, and only a few patients ultimately benefit from this approach. Here, we discuss the potential of EGFR-TKIs for inducing antitumor immunity and the feasibility of their combination with immunotherapy (including PD-1/PD-L1 inhibitors) in NSCLC patients and the associated challenges for clinical application.

SUBMITTER: Liang H

PROVIDER: S-EPMC6163004 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Project description: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.

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Immunotherapy combined with epidermal growth factor receptor-tyrosine kinase inhibitors in non-small-cell lung cancer treatment.

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