Ge Yan, Zhao Yang
Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Discov Oncol. 2025 Jun 18;16(1):1148. doi: 10.1007/s12672-025-02926-0.
Driver gene-negative advanced non-squamous non-small cell lung cancer (NSCLC) exhibits inherent resistance to conventional therapies, representing a significant treatment challenge. The limited efficacy of platinum-based chemotherapy alone underscores the need for resistance-mitigating strategies. Camrelizumab, a PD-1 immune checkpoint inhibitor, may overcome resistance mechanisms by restoring immune surveillance and enhancing chemosensitivity through immunogenic cell death (ICD) and T-cell activation. This study investigates how this combination counters therapeutic resistance in real-world clinical settings.
This propensity score-matched retrospective cohort study evaluated 106 patients with advanced non-squamous NSCLC lacking driver mutations, comparing Camrelizumab plus chemotherapy (pemetrexed + cisplatin) versus chemotherapy alone. The median follow-up duration was 15.2 months (range 6.5-24.8 months). Progression-free survival (PFS) was the primary endpoint, with objective response rate (ORR), resistance patterns, and treatment-related adverse events as secondary outcomes. PD-L1 expression levels and tumor mutational burden (TMB) data were not available for this cohort. Multivariate Cox regression analysis was performed to adjust for potential confounders.
Combination therapy significantly overcame resistance to conventional treatment, prolonging median PFS (9.8 vs. 5.7 months, HR = 0.48, P = 0.010) and improving ORR (47.1% vs. 39.6%, P = 0.007). Multivariate Cox regression confirmed the PFS benefit (adjusted HR = 0.51, 95% CI 0.29-0.89, P = 0.018). Notably, patients with early progression on prior chemotherapy regimens (resistant phenotype) demonstrated meaningful clinical benefit from the addition of immunotherapy. Immune-related adverse events were managed with corticosteroids and treatment interruptions per established guidelines. Immunotherapy-specific adverse events were observed but manageable, suggesting a favorable risk-benefit profile in overcoming treatment resistance. Overall survival data were immature at the time of analysis.
Camrelizumab-chemotherapy combination effectively addresses resistance mechanisms in driver-negative NSCLC through immune microenvironment modulation. However, the study's limitations include small sample size (53 patients per group), retrospective design, and absence of biomarker data. These findings illuminate a promising strategy for overcoming the therapeutic plateau reached with conventional chemotherapy. This real-world evidence supports further investigation into resistance biomarkers and adaptive treatment algorithms to optimize immunotherapy integration in resistant NSCLC. Prospective studies with larger cohorts are warranted to confirm these findings.
Not applicable.
驱动基因阴性的晚期非鳞状非小细胞肺癌（NSCLC）对传统疗法表现出内在抗性，这是一个重大的治疗挑战。单纯铂类化疗的疗效有限，凸显了减轻抗性策略的必要性。卡瑞利珠单抗是一种PD-1免疫检查点抑制剂，可通过恢复免疫监视以及通过免疫原性细胞死亡（ICD）和T细胞激活增强化疗敏感性来克服抗性机制。本研究调查了这种联合疗法在真实世界临床环境中如何对抗治疗抗性。
这项倾向评分匹配的回顾性队列研究评估了106例缺乏驱动基因突变的晚期非鳞状NSCLC患者，比较了卡瑞利珠单抗联合化疗（培美曲塞+顺铂）与单纯化疗。中位随访时间为15.2个月（范围6.5 - 24.8个月）。无进展生存期（PFS）是主要终点，客观缓解率（ORR）、抗性模式和治疗相关不良事件为次要结局。该队列无法获得PD-L1表达水平和肿瘤突变负荷（TMB）数据。进行多变量Cox回归分析以调整潜在混杂因素。
联合疗法显著克服了对传统治疗的抗性，延长了中位PFS（9.8个月对5.7个月，HR = 0.48，P = 0.010）并提高了ORR（47.1%对39.6%，P = 0.007）。多变量Cox回归证实了PFS获益（调整后HR = 0.51，95% CI 0.29 - 0.89，P = 0.018）。值得注意的是，先前化疗方案早期进展的患者（抗性表型）从添加免疫疗法中获得了有意义的临床益处。免疫相关不良事件按照既定指南用皮质类固醇和治疗中断进行处理。观察到了免疫疗法特异性不良事件但可管理，表明在克服治疗抗性方面风险效益比良好。分析时总生存数据不成熟。
卡瑞利珠单抗 - 化疗联合疗法通过调节免疫微环境有效解决了驱动基因阴性NSCLC中的抗性机制。然而，该研究的局限性包括样本量小（每组53例患者）、回顾性设计以及缺乏生物标志物数据。这些发现阐明了一种克服传统化疗所达到的治疗平台期的有前景策略。这一真实世界证据支持进一步研究抗性生物标志物和适应性治疗算法，以优化抗性NSCLC中的免疫疗法整合。有必要进行更大队列的前瞻性研究以证实这些发现。
不适用。
