Department of Thoracic Oncology, Thoraxklinik and National Center for Tumor Diseases at Heidelberg University Hospital, Heidelberg, Germany; German Center for Lung Research (DZL), Germany.
Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Eur J Cancer. 2022 Jul;170:106-118. doi: 10.1016/j.ejca.2022.04.020. Epub 2022 May 20.
EGFR exon20 insertions (ex20ins) are targeted by novel compounds in non-small-cell lung cancer (NSCLC). However, data about outcome under conventional therapies and the influence of molecular features are scarce.
We retrospectively analysed 118 patients with evaluation of radiologic response based on RECIST v1.1. TP53 status was available for 88 cases.
Platinum doublets and chemoimmunotherapy showed similar response rates (20-25%), disease control rates (80%) and median progression-free survival (mPFS, ≈7 months), which were longer compared to monochemotherapy (9%, 59%, 4.1 months), EGFR inhibitors (0%, 46%, 3.0) and PD-(L)1 inhibitors (0%, 30%, 2.1; p < 0.05). Overall survival (OS) was not dependent on the choice of first-line treatment, but related to more lines of systemic therapy (p < 0.05). TP53 mutations and brain metastases were associated with shorter PFS under platinum doublets and EGFR inhibitors (HR 3.3-6.1, p < 0.01), and shorter OS for patients receiving both treatments (p < 0.05). More tumour CD8 and less Th1 cells were associated with longer OS independent of brain and TP53 status (p < 0.01). No difference in outcome was noted according to the ex20ins site and use of pemetrexed (vs. other cytotoxics) or bevacizumab. Long-lasting responses (>1 year) occasionally occurred under EGFR inhibitors for both 'near-' and 'far-loop' variants.
Platinum doublets and chemoimmunotherapy have the highest activity with ORR of 20-25% and mPFS of approximately 7 months, regardless of the cytotoxic partner, while PD-(L)1 inhibitors show limited efficacy. TP53 mutations, brain metastases and a lower tumour CD8/Th1-cell ratio are independently associated with shorter survival.
表皮生长因子受体外显子 20 插入（ex20ins）可被新型化合物靶向治疗非小细胞肺癌（NSCLC）。然而，关于传统疗法的疗效和分子特征的影响的数据还很缺乏。
我们回顾性分析了 118 例患者，根据 RECIST v1.1 评估了放射学反应。TP53 状态可用于 88 例患者。
铂类双药和化疗免疫治疗的缓解率（20-25%）、疾病控制率（80%）和中位无进展生存期（mPFS，约 7 个月）相似，与单药化疗（9%、59%、4.1 个月）、EGFR 抑制剂（0%、46%、3.0 个月）和 PD-（L）1 抑制剂（0%、30%、2.1 个月）相比，差异有统计学意义（p<0.05）。总生存期（OS）并不依赖于一线治疗的选择，但与更多线的系统治疗有关（p<0.05）。TP53 突变和脑转移与铂类双药和 EGFR 抑制剂的 PFS 缩短有关（HR 3.3-6.1，p<0.01），与接受两种治疗的患者的 OS 缩短有关（p<0.05）。更多的肿瘤 CD8 和更少的 Th1 细胞与独立于脑转移和 TP53 状态的 OS 延长有关（p<0.01）。根据 ex20ins 部位、培美曲塞（与其他细胞毒药物相比）或贝伐珠单抗的使用，结果没有差异。在 EGFR 抑制剂下，“近环”和“远环”变异的长期缓解（>1 年）偶尔发生。
铂类双药和化疗免疫治疗的活性最高，ORR 为 20-25%，mPFS 约为 7 个月，与细胞毒性药物无关，而 PD-（L）1 抑制剂的疗效有限。TP53 突变、脑转移和较低的肿瘤 CD8/Th1 细胞比例与较短的生存期独立相关。
