程序性死亡蛋白1（PD-1）/程序性死亡配体1（PD-L1）抑制剂联合安罗替尼用于广泛期小细胞肺癌二线治疗的疗效
Efficacy of PD-(L)1 inhibitors plus anlotinib in the second-line treatment of extensive-stage small cell lung cancer.
作者信息
Zhang Jian, Wu Zijie, Wang Shuyun, Sun Yanxin, Wu Jiake, Wang Dahai, Ge Yihui, Li Juan, Sun Haifeng, Cheng Qinglei, Gao Aiqin, Sun Yuping
机构信息
Phase I Clinical Research Center, Shandong Cancer Hospital and Institute, Zhangqiu District People's Hospital, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China.
Phase I Clinical Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan, 250117, Shandong, China.
出版信息
BMC Cancer. 2025 Jul 1;25(1):1070. doi: 10.1186/s12885-025-14458-5.
BACKGROUND
The efficacy of second-line therapy for extensive-stage small cell lung cancer (ES-SCLC) is still limited, with the PFS of 2-3 months. Given the synergistic effect of PD-(L)1 inhibitors and anti-angiogenic agents, their combination represents a novel and promising strategy to reprogram the protumoral microenvironment and improve patient outcome. However, the efficacy of PD-(L)1 inhibitors plus anlotinib as the second-line treatment of ES-SCLC is undetermined in the real world.
METHODS
We retrospectively analyzed 389 ES-SCLC patients from 3 cancer centers. All the patients received one of the following second-line schemes: PD-(L)1 inhibitors plus anlotinib (I + A), PD-(L)1 inhibitors plus chemotherapy (I + C), or chemotherapy alone (C). The efficacy, including the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety were compared among the three groups. We also analyzed the impact of first-line immune checkpoint inhibitors (ICIs) on the efficacy of second-line I + A.
RESULTS
The baseline clinical characteristics among three groups were largely balanced. I + A treatment demonstrated significantly higher ORR (30.2%) and DCR (82.6%) compared with I + C (ORR = 17.6%, DCR = 68.8%) and C (ORR = 18.0%, DCR = 53.9%). Furthermore, I + A group showed the longest mPFS (7.2 months) and mOS (33.5 months), compared to I + C (mPFS = 4.6 months, mOS = 19.0 months, both P < 0.001) and C (mPFS = 3.4 months, P < 0.01; mOS = 18.3 months, P = 0.083). The benefit of I + A treatment persists independent of the administration of first-line ICIs. A stratified analysis revealed that female patients and those with oligometastasis (≤ 3 metastatic sites) benefit more from I + A treatment than male patients and those with polymetastasis. In terms of safety, I + A group displayed the lowest incidence of ≥ grade 3 myelosuppression compared to the I + C and C groups (3.5% vs. 11.2% vs. 16.3%, P < 0.01). However, I + A treatment was associated with a higher prevalence of immune-related pneumonia (2.3% vs. 0% vs. 0%, P < 0.05) and hemoptysis (1.4% vs. 0% vs. 0.6%, P < 0.05) compared to I + C and C treatment.
CONCLUSIONS
PD-(L)1 inhibitors and anlotinib has promising efficacy and manageable toxicity as the second-line therapy of ES-SCLC.
背景
广泛期小细胞肺癌（ES-SCLC）二线治疗的疗效仍然有限，无进展生存期（PFS）为2至3个月。鉴于PD-(L)1抑制剂与抗血管生成药物的协同作用，它们的联合应用代表了一种重塑肿瘤微环境并改善患者预后的新颖且有前景的策略。然而，在现实世界中，PD-(L)1抑制剂联合安罗替尼作为ES-SCLC二线治疗的疗效尚不确定。
方法
我们回顾性分析了来自3个癌症中心的389例ES-SCLC患者。所有患者接受以下二线治疗方案之一：PD-(L)1抑制剂联合安罗替尼（I+A）、PD-(L)1抑制剂联合化疗（I+C）或单纯化疗（C）。比较三组的疗效，包括客观缓解率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）、总生存期（OS）和安全性。我们还分析了一线免疫检查点抑制剂（ICI）对二线I+A疗效的影响。
结果
三组的基线临床特征基本平衡。与I+C（ORR=17.6%，DCR=68.8%）和C（ORR=18.0%，DCR=53.9%）相比，I+A治疗显示出显著更高的ORR（30.2%）和DCR（82.6%）。此外，与I+C（mPFS=4.6个月，mOS=19.0个月，P均<0.001）和C（mPFS=3.4个月，P<0.01；mOS=18.3个月，P=0.083）相比，I+A组的中位PFS最长（7.2个月），中位OS最长（33.5个月）。I+A治疗的益处与一线ICI的使用无关。分层分析显示，女性患者和寡转移（≤3个转移部位）患者比男性患者和多转移患者从I+A治疗中获益更多。在安全性方面，与I+C组和C组相比，I+A组≥3级骨髓抑制的发生率最低（3.5%对11.2%对16.3%，P<0.01）。然而，与I+C和C治疗相比I+A治疗相关的免疫相关性肺炎（2.3%对0%对0%，P<0.05）和咯血（1.4%对0%对0.6%，P<0.05）的发生率更高。
结论
PD-(L)1抑制剂与安罗替尼作为ES-SCLC的二线治疗具有有前景的疗效和可管理的毒性。
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