Background/Objectives: Several genetic alterations have been identified as drivers of uncontrolled cell growth in lung cancer, with KRAS mutations representing the most prevalent driver oncogene. Despite advances in targeted treatment, the 5-year survival rate of patients with advanced/metastatic NSCLC is still less than 20%. This study aims to assess the clinical relevance of KRAS mutations in the context of PD-L1 expression, focusing on patients with PD-L1 Tumor Proportion Score (TPS) ≥ 50% and treated with first-line immune checkpoint inhibitors (ICIs). Methods: We conducted a retrospective analysis of a real-world cohort comprising all staged NSCLC patients diagnosed and treated between 2018 and 2022 at our Institution with the available Next Generation Sequencing and PD-L1 immunohistochemistry results. Statistical analyses were made using the log-rank test, the two-tailed Fisher’s exact test, and Kaplan–Meier survival curves. Results: Among 520 NSCLC patients, 288 were adenocarcinoma (AC). Of these, 110/288 (38.2%) were KRAS mutants, and 83/278 (29.8%) presented a PD-L1 TPS ≥ 50%. In this subgroup, KRAS mutants demonstrated longer median overall survival (mOS) and progression-free survival (PFS) compared to the KRAS wild-type (28.7 vs. 10.7 months,p= 0.010; 6.4 vs. 3.5 months,p= 0.005, respectively). While OS did not differ among KRAS mutation subtypes, PFS was significantly shorter in patients with p.G12D (3.5 months,p= 0.03). Conclusion: This study is the first to investigate the interplay between KRAS mutations and PD-L1 expression in a real-world stage IV lung AC cohort treated with ICIs. Our findings indicate that the p.G12D mutation is associated with an extremely severe disease upon ICI monotherapy. These preliminary results need further validation in larger, prospective cohorts.
背景/目的：在肺癌中，多种基因改变已被确定为驱动细胞失控生长的因素，其中KRAS突变是最常见的驱动癌基因。尽管靶向治疗取得了进展，但晚期/转移性非小细胞肺癌患者的5年生存率仍低于20%。本研究旨在评估KRAS突变在PD-L1表达背景下的临床相关性，重点关注PD-L1肿瘤比例评分≥50%且接受一线免疫检查点抑制剂治疗的患者。方法：我们对2018年至2022年间在本机构诊断并治疗的所有分期非小细胞肺癌患者进行了回顾性分析，这些患者均具备可用的下一代测序和PD-L1免疫组化结果。统计分析采用对数秩检验、双尾Fisher精确检验和Kaplan-Meier生存曲线。结果：在520例非小细胞肺癌患者中，288例为腺癌。其中，110/288例（38.2%）为KRAS突变型，83/278例（29.8%）的PD-L1 TPS≥50%。在该亚组中，与KRAS野生型相比，KRAS突变型患者的中位总生存期和无进展生存期更长（分别为28.7个月 vs. 10.7个月，p=0.010；6.4个月 vs. 3.5个月，p=0.005）。虽然不同KRAS突变亚型之间的总生存期无差异，但p.G12D突变患者的无进展生存期显著缩短（3.5个月，p=0.03）。结论：本研究首次在真实世界接受免疫检查点抑制剂治疗的IV期肺腺癌队列中探讨了KRAS突变与PD-L1表达之间的相互作用。我们的研究结果表明，p.G12D突变与接受免疫检查点抑制剂单药治疗的极严重疾病相关。这些初步结果需要在更大规模的前瞻性队列中进一步验证。
肿瘤(癌症)患者之家