Department of Thoracic Oncology, Aichi Cancer Center Hospital, 1-1, Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan.
BMC Cancer. 2024 Jul 15;24(1):842. doi: 10.1186/s12885-024-12554-6.
Targeted therapy is now the standard of care in driver-oncogene-positive non-small cell lung cancer (NSCLC). Its initial clinical effects are remarkable. However, almost all patients experience treatment resistance to targeted therapy. Hence, chemotherapy is considered a subsequent treatment option. In patients with driver-oncogene-negative NSCLC, combined immune checkpoint inhibitors (ICIs) and chemotherapy as the first-line therapy has been found to be beneficial. However, the efficacy of ICI plus chemotherapy against driver-oncogene-positive NSCLC other than epidermal growth factor receptor mutation and anaplastic lymphoma kinase fusion is unclear.
Using the hospital medical records, we retrospectively reviewed advanced or recurrent NSCLC patients who were treated with chemotherapy with or without ICIs at Aichi Cancer Center Hospital between January 2014 and January 2023. Patients with druggable rare mutations such as KRAS-G12C, MET exon 14 skipping, HER2 20 insertion, BRAF-V600E mutations, and ROS1 and RET rearrangements were analyzed.
In total, 61 patients were included in this analysis. ICI plus chemotherapy was administered in 36 patients (the ICI-chemo group) and chemotherapy in 25 patients (the chemo group). The median progression-free survival (PFS) rates were 14.0 months in the ICI-chemo group and 4.8 months in the chemo group (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.28-1.01). The median overall survival rates were 31.3 and 21.7 months in the ICI-chemo and chemo groups, respectively (HR = 0.70, 95% CI = 0.33-1.50). Multivariate Cox regression analysis of PFS revealed that HER2 exon 20 insertion mutation was significantly associated with a poorer PFS (HR: 2.39, 95% CI: 1.19-4.77, P = 0.014). Further, ICI-chemo treatment was significantly associated with a better PFS (HR: 0.48, 95% CI: 0.25-0.91, P = 0.025).
ICI plus chemotherapy improves treatment efficacy in rare driver-oncogene-positive NSCLC.
在驱动基因突变阳性非小细胞肺癌（NSCLC）中，靶向治疗目前是标准治疗方法。其初始临床效果显著。然而，几乎所有患者都会对靶向治疗产生耐药性。因此，化疗被认为是后续的治疗选择。在驱动基因突变阴性的 NSCLC 患者中，联合免疫检查点抑制剂（ICI）和化疗作为一线治疗已被证明是有益的。然而，ICI 联合化疗对除表皮生长因子受体突变和间变性淋巴瘤激酶融合以外的驱动基因突变阳性 NSCLC 的疗效尚不清楚。
使用医院病历，我们回顾性分析了 2014 年 1 月至 2023 年 1 月期间在爱知县癌症中心医院接受化疗联合或不联合 ICI 治疗的晚期或复发性 NSCLC 患者。分析了具有可用药的罕见突变（如 KRAS-G12C、MET 外显子 14 跳跃、HER2 20 插入、BRAF-V600E 突变和 ROS1 和 RET 重排）的患者。
共有 61 例患者纳入本分析。36 例患者（ICI-化疗组）接受了 ICI 联合化疗，25 例患者（化疗组）接受了单纯化疗。ICI-化疗组的中位无进展生存期（PFS）为 14.0 个月，化疗组为 4.8 个月（风险比[HR] = 0.54，95%置信区间[CI] = 0.28-1.01）。ICI-化疗组和化疗组的中位总生存期分别为 31.3 个月和 21.7 个月（HR = 0.70，95% CI = 0.33-1.50）。PFS 的多变量 Cox 回归分析显示，HER2 外显子 20 插入突变与较差的 PFS 显著相关（HR：2.39，95% CI：1.19-4.77，P = 0.014）。此外，ICI-化疗治疗与更好的 PFS 显著相关（HR：0.48，95% CI：0.25-0.91，P = 0.025）。
ICI 联合化疗可提高罕见驱动基因突变阳性 NSCLC 的治疗效果。
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