Department of Medical Oncology, Tianjin Medical University General Hospital, Tianjin, China.
Thorac Cancer. 2024 Sep;15(25):1842-1853. doi: 10.1111/1759-7714.15408. Epub 2024 Jul 30.
Homologous recombination deficiency (HRD) is a biomarker that predicts response to ovarian cancer treatment with poly (ADP-ribose) polymerase (PARP) inhibitors or breast cancer treatment with first-line platinum-based chemotherapy. However, there are few studies on the prognosis of lung cancer patients treated with immune checkpoint inhibitor (ICI) therapy using HRD as a biomarker.
We studied the relationship between HRD status and the effectiveness of first-line ICI-based therapy in EGFR/ALK wild-type metastatic non-small cell lung cancer patients (NSCLC) patients.
This study included 22 treatment naïve NSCLC patients. The HRD score ranged from -26.37 to 92.34, with an average of 24.57. Based on analysis of the progression-free survival (PFS) data from the included NSCLC patients, threshold traversal was carried out. HRD (+) was defined as an HRD score of 31 or higher. Kaplan-Meier PFS survival analysis showed prolonged median PFS (mPFS) in NSCLC patients with HRD (+) versus HRD (-) (N/A vs. 7.0 ms, log-rank p = 0.029; HR 0.20, 95% CI: 0.04-0.96, likelihood-ratio p = 0.03). In patients with PD-L1 TPS ≥50% and HRD score ≥31 (co-status high), the mPFS was temporarily not reached during the follow-up period. In patients with PD-L1 TPS <1% and HRD score <31, the mPFS was 3 ms. Cox regression analysis showed that the hazard ratio of the co-status was 0.14 (95% CI: 0.04-0.54), which was a good prognostic factor, and the prognostic effect of co-status was better than that of HRD score alone.
The HRD status can be identified as an independent significance in NSCLC patients treated with first-line ICI-based therapy.
同源重组缺陷（HRD）是预测卵巢癌治疗中聚（ADP-核糖）聚合酶（PARP）抑制剂或乳腺癌治疗中一线铂类化疗反应的生物标志物。然而，关于将 HRD 作为生物标志物用于预测接受免疫检查点抑制剂（ICI）治疗的肺癌患者预后的研究较少。
我们研究了 HRD 状态与 EGFR/ALK 野生型转移性非小细胞肺癌（NSCLC）患者一线基于 ICI 的治疗效果之间的关系。
本研究纳入了 22 例初治 NSCLC 患者。HRD 评分范围为-26.37 至 92.34，平均 24.57。根据纳入的 NSCLC 患者的无进展生存期（PFS）数据分析，进行了阈值跨越。将 HRD（+）定义为 HRD 评分≥31。Kaplan-Meier PFS 生存分析显示，HRD（+）的 NSCLC 患者中位 PFS（mPFS）长于 HRD（-）患者（N/A 比 7.0 ms，对数秩检验 P=0.029；HR 0.20，95%CI：0.04-0.96，似然比检验 P=0.03）。在 PD-L1 TPS≥50%和 HRD 评分≥31（共状态高）的患者中，在随访期间未达到 mPFS。在 PD-L1 TPS<1%和 HRD 评分<31 的患者中，mPFS 为 3 ms。Cox 回归分析显示，共状态的风险比为 0.14（95%CI：0.04-0.54），是一个良好的预后因素，共状态的预后效果优于 HRD 评分单独。
HRD 状态可作为 NSCLC 患者一线 ICI 治疗的独立指标。
