Wu Mingying, Zhou Na, Guan Mei, Wang Yingyi, Wang Yuzhou
Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
Department of Oncology, Centro Hospitalar Conde de Sao Januario, Estrada do Visconde de S. Januario, Macau, China.
Lung Cancer. 2025 Jan;199:108068. doi: 10.1016/j.lungcan.2024.108068. Epub 2024 Dec 25.
Pulmonary sarcomatoid carcinoma (PSC) is a rare, heterogeneous subgroup of non-small cell lung cancer (NSCLC). Patients with advanced PSCs have poor survival due to resistance to chemotherapy and radiotherapy, and narrow access to targeted therapy. Immune checkpoint inhibitors (ICIs) offer new hope, whereas data on their effectiveness is limited.
This retrospective study collected medical records of patients with advanced PSCs from January 2010 to March 2024 across two centers in China, analyzing demographic, treatment, and survival data. Sixty cases were included.
In tumors tested for PD-L1 expression, 80 % had PD-L1 positivity, and 60 % exhibited TPS ≥ 50 %. The most frequently mutated genes in PSCs were TP53 (25.9 %), KRAS (22.8 %), MET (7.4 %), BRAF (7.4 %), CDKN2A/B (7.4 % each), and EGFR (6.2 %). Median OS of patients with advanced PSCs receiving anti-PD-1 or anti-PD-L1 antibodies in any line was significantly longer compared to those who did not (NR vs. 11.2 months, p = 0.015). ICI application was an independent favorable factor for the prognosis of patients diagnosed with advanced PSC (HR 0.32, p = 0.008). In the subgroup treated with ICI-based therapies, ORR and DCR were 34.5 % and 82.8 %, respectively. The mPFS and mOS of ICI-based therapies were 12.5 and 16.0 months, respectively. TP53 mutations and PD-L1 TPS ≥ 80 % were associated with prolonged PFS (p = 0.021, p = 0.035) and OS (p = 0.013 and p = 0.018).
Positive or high PD-L1 expression was prevalent in advanced PSCs. Anti-PD-1 or anti-PD-L1 antibodies were associated with favorable prognosis, and should be considered a key treatment option for patients with advanced PSC lacking actionable driver mutations. In addition to PD-L1 expression, TP53 mutations have the potential to predict the efficacy of ICIs in treating patients with advanced PSC and its prognostic significance deserves further validation in larger prospective studies.
肺肉瘤样癌（PSC）是一种罕见的、异质性的非小细胞肺癌（NSCLC）亚组。晚期PSC患者由于对化疗和放疗耐药且难以获得靶向治疗，生存情况较差。免疫检查点抑制剂（ICI）带来了新的希望，但其有效性的数据有限。
这项回顾性研究收集了2010年1月至2024年3月期间中国两个中心的晚期PSC患者的病历，分析了人口统计学、治疗和生存数据。共纳入60例患者。
在检测PD-L1表达的肿瘤中，80%为PD-L1阳性，60%的肿瘤细胞比例（TPS）≥50%。PSC中最常发生突变的基因是TP53（25.9%）、KRAS（22.8%）、MET（7.4%）、BRAF（7.4%）、CDKN2A/B（各7.4%）和EGFR（6.2%）。接受过任何一线抗PD-1或抗PD-L1抗体治疗的晚期PSC患者的中位总生存期（OS）显著长于未接受过此类治疗的患者（未达到中位生存期与11.2个月，p = 0.015）。ICI应用是诊断为晚期PSC患者预后的独立有利因素（风险比0.32，p = 0.008）。在接受基于ICI治疗的亚组中，客观缓解率（ORR）和疾病控制率（DCR）分别为34.5%和82.8%。基于ICI治疗的中位无进展生存期（mPFS）和中位总生存期（mOS）分别为12.5个月和16.0个月。TP53突变和PD-L1 TPS≥80%与更长的无进展生存期（p = 0.021，p = 0.035）和总生存期（p = 0.013和p = 0.018）相关。
晚期PSC中PD-L1阳性或高表达普遍存在。抗PD-1或抗PD-L1抗体与良好的预后相关，对于缺乏可靶向驱动基因突变的晚期PSC患者应考虑作为关键治疗选择。除了PD-L1表达外，TP53突变有可能预测ICI治疗晚期PSC患者的疗效，其预后意义值得在更大规模的前瞻性研究中进一步验证。
