Division of Hematology and Oncology, Department of Internal Medicine, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, MI, USA.
Department of Internal Medicine, Henry Ford Health System, Detroit, MI, USA.
Target Oncol. 2022 Mar;17(2):187-192. doi: 10.1007/s11523-022-00873-2. Epub 2022 Mar 21.
Human epidermal growth factor receptor 2 (ERBB2) mutation is a known oncogenic driver mutation in a small proportion of non-small cell lung cancers (NSCLCs). Many targeted therapies are being developed and investigated for the treatment of ERBB2-mutated NSCLC, however none of these agents have yet been approved as a front-line treatment. Thus, platinum-based chemotherapy with or without immunotherapy remains the preferred first-line therapy for ERBB2-mutated NSCLC.
We aimed to study the activity of chemotherapy in combination with pembrolizumab as first-line treatment in patients with stage IV ERBB2-mutated NSCLC.
We retrospectively identified five patients with ERBB2-mutated NSCLC treated with carboplatin, pemetrexed and pembrolizumab as first-line therapy between 2018 and 2020. Overall survival (OS), progression-free survival (PFS), and time to next therapy (TTNT) were summarized by Kaplan-Meier methodology using R 4.0.5 with median time to event. Response rates defined by partial response (PR) or PR + stable disease (SD) and 95% Clopper-Pearson confidence interval (CI) were calculated.
The median age of these five patients was 60 years and all five patients' tumors had ERBB2 mutations-4 had exon 20 mutation and 1 had exon 23 mutation. With a median follow-up of 32 months, the median OS was 24 months, the median PFS was 9 months, and the median TTNT was 9 months. The response rate was 0.6 for PR (Clopper-Pearson exact 95% CI 0.147-0.947) and 0.8 for PR and SD (Clopper-Pearson exact 95% CI 0.284-0.995). No unexpected toxicities were observed.
In a small number of patients, chemotherapy and pembrolizumab as first-line therapy in ERBB2-mutated NSCLC patients demonstrated activity similar to previous reports with this regimen. Future clinical trials are needed to determine the role of chemotherapy and immunotherapy for this patient population in the context of emerging targeted agents.
人类表皮生长因子受体 2（ERBB2）突变是一小部分非小细胞肺癌（NSCLC）的已知致癌驱动突变。许多针对 ERBB2 突变 NSCLC 的靶向治疗药物正在被开发和研究，但这些药物都尚未被批准作为一线治疗药物。因此，含铂化疗联合或不联合免疫治疗仍然是 ERBB2 突变 NSCLC 的首选一线治疗。
我们旨在研究化疗联合帕博利珠单抗作为 ERBB2 突变 IV 期 NSCLC 患者一线治疗的疗效。
我们回顾性地鉴定了 2018 年至 2020 年间接受卡铂、培美曲塞和帕博利珠单抗作为一线治疗的 5 例 ERBB2 突变 NSCLC 患者。使用 R 4.0.5 中的 Kaplan-Meier 方法总结总生存期（OS）、无进展生存期（PFS）和下一次治疗时间（TTNT），使用事件中位数时间进行分析。通过部分缓解（PR）或 PR+稳定疾病（SD）和 95%Clop-Pearson 置信区间（CI）计算缓解率。
这 5 例患者的中位年龄为 60 岁，所有 5 例患者的肿瘤均有 ERBB2 突变-4 例患者有外显子 20 突变，1 例患者有外显子 23 突变。中位随访 32 个月时，中位 OS 为 24 个月，中位 PFS 为 9 个月，中位 TTNT 为 9 个月。PR 的缓解率为 0.6（Clop-Pearson 确切 95%CI 0.147-0.947），PR 和 SD 的缓解率为 0.8（Clop-Pearson 确切 95%CI 0.284-0.995）。未观察到意外毒性。
在少数患者中，化疗联合帕博利珠单抗作为 ERBB2 突变 NSCLC 患者的一线治疗显示出与该方案既往报告相似的活性。未来的临床试验需要确定化疗和免疫疗法在新兴靶向药物背景下对这一患者群体的作用。
