Efficacy of immune checkpoint inhibitor therapy in EGFR mutation-positive patients with NSCLC and brain metastases who have failed EGFR-TKI therapy.
Efficacy of immune checkpoint inhibitor therapy in EGFR mutation-positive patients with NSCLC and brain metastases who have failed EGFR-TKI therapy.
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DOI：
10.3389/fimmu.2022.955944
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发表时间：
2022
影响因子：
7.3
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中科院分区：
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对于既往接受EGFR酪氨酸激酶抑制剂（EGFR-TKI）治疗后进展的EGFR突变型非小细胞肺癌（NSCLC）脑转移（BM），几乎没有治疗选择。本研究旨在评估免疫检查点抑制剂（ICI）治疗在这些患者中的疗效。回顾性分析了经证实的敏感EGFR突变和BM的NSCLC患者。所有患者均经历了EGFR-TKI治疗失败，并根据后续治疗分为两个队列。队列1包括接受ICI治疗的患者，而队列2包括接受化疗的患者。使用总体和颅内客观缓解率（ORR）评价治疗缓解。通过Kaplan-Meier分析计算总体和颅内无进展生存期（PFS），并与对数秩检验进行比较。单因素和多因素考克斯分析用于确定预后因素。队列1和队列2分别纳入了53例接受ICI治疗的患者和40例接受化疗的患者。在队列1中，总体ORR为20.8%，中位总体PFS为4.2个月。中位颅内PFS为5.1个月。在38例具有可测量颅内病变的患者中，颅内ORR为21.0%。接受ICI联合化疗的患者的颅内ORR最高，为37.5%。与队列2中接受化疗的患者相比，接受ICI联合化疗的患者的颅内PFS（6.4 vs. 5.1个月，p = 0.110）和总体PFS（6.2 vs. 4.6个月，p = 0.054）均较长，这些差异接近统计学显著性。单变量和多变量考克斯分析表明，高疾病负荷（p = 0.019）、既往第三代EGFR-TKI治疗（p = 0.019）和肺免疫预后指数（LIPI）差（p = 0.012）是总体PFS的独立阴性预测因素，在接受ICI治疗的患者中，多种BM与颅内PFS呈负相关。我们的研究结果表明，ICI联合化疗具有有效的颅内疗效，可能是既往EGFR-TKI治疗失败的EGFR突变型NSCLC BM患者的一种有希望的治疗候选药物。
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.