Ksienski Doran, Truong Pauline T, Bone Jeffrey N, Egli Sarah, Clarkson Melissa, Patterson Tiffany, Lesperance Mary, Lakkunarajah Suganija
BC Cancer-Victoria, 2410 Lee Avenue V8R 6V5, Victoria, BC, Canada.
University of British Columbia, Victoria, BC, Canada.
Target Oncol. 2025 Jan;20(1):149-160. doi: 10.1007/s11523-024-01111-7. Epub 2024 Nov 4.
Concurrent chemoradiotherapy (cCRT) followed by 1 year of the immune checkpoint inhibitor (ICI) durvalumab is standard of care for patients with unresectable stage III nonsmall cell lung cancer (NSCLC).
The purpose of this study was to evaluate survival outcomes of (1) cCRT followed by durvalumab in patients older versus younger than 75 years of age and (2) post-progression treatment with ICI alone versus chemotherapy alone versus combined ICI and chemotherapy.
Patients with unresectable stage III NSCLC treated between January 2018 and July 2023 with cCRT followed by durvalumab were identified retrospectively. Progression-free survival (PFS) and overall survival (OS) from ICI start were analyzed in three cohorts aged < 65, 65-74, and ≥ 75 years. Multivariable Cox proportional hazard regression modelling of factors associated with OS was undertaken. Logistic regression analysis identified risk factors of early durvalumab discontinuation for toxicity. Time from first salvage drug treatment to death (OS-2) was described.
A total of 472 patients were analyzed: the proportions aged < 65, 65-74, and ≥ 75 years were 34.3%, 42.8%, and 22.9%, respectively. Odds of early durvalumab discontinuation was 2.2-fold greater in the oldest (versus youngest) cohort. Age associated differences in median PFS (26.7 months, 20.3 months, and 14.2 months; p < 0.001) and OS (60.8 months, 44.4 months, and 27.6 months; p < 0.001) were observed. On multivariable analysis, factors associated with shorter OS were age ≥ 75 years (versus < 65), performance status 2/3 (versus 0/1), stage IIIC (versus IIIA), neutrophil to lymphocyte ratio (per 7.43 unit increase), Charlson comorbidity index (per 1 unit increase), tumoral PD-L1 expression < 1% (versus ≥ 50%, 1-49%, or unknown), and squamous histology (versus non-squamous). Of 264 patients with disease progression, 48.5% received subsequent drug therapy. Median OS-2 was longer with ICI alone (9.9 months) or ICI-chemotherapy (11.8 months) than platinum doublet chemotherapy (6.7 months.) For recurrences < 6 months from the last durvalumab infusion, OS-2 were similar across treatment groups.
In the studied cohort, OS was significantly shorter for patients ≥ 75 years of age treated with cCRT followed by durvalumab compared to those < 65 years. Post-progression systemic therapy was associated with modest efficacy, underscoring the need for new therapies.
同步放化疗（cCRT）后使用免疫检查点抑制剂（ICI）度伐利尤单抗治疗1年是不可切除的III期非小细胞肺癌（NSCLC）患者的标准治疗方案。
本研究的目的是评估（1）cCRT后使用度伐利尤单抗治疗的75岁及以上与75岁以下患者的生存结局，以及（2）疾病进展后单独使用ICI与单独使用化疗以及ICI与化疗联合治疗的效果。
回顾性纳入2018年1月至2023年7月期间接受cCRT后使用度伐利尤单抗治疗的不可切除III期NSCLC患者。分析年龄＜65岁、65 - 74岁和≥75岁三个队列从开始使用ICI起的无进展生存期（PFS）和总生存期（OS）。对与OS相关的因素进行多变量Cox比例风险回归建模。逻辑回归分析确定因毒性而提前停用度伐利尤单抗的危险因素。描述从首次挽救性药物治疗到死亡的时间（OS-2）。
共分析了472例患者：年龄＜65岁、65 - 74岁和≥75岁的患者比例分别为34.3%、42.8%和22.9%。最年长队列（与最年轻队列相比）提前停用度伐利尤单抗的几率高2.2倍。观察到年龄相关的中位PFS（26.7个月、20.3个月和14.2个月；p＜0.001）和OS（60.8个月、44.4个月和27.6个月；p＜0.001）差异。多变量分析显示，与较短OS相关的因素包括年龄≥75岁（与＜65岁相比）、体能状态为2/3（与0/1相比）、IIIC期（与IIIA期相比）、中性粒细胞与淋巴细胞比值（每增加7.43个单位）、Charlson合并症指数（每增加1个单位）、肿瘤PD-L1表达＜1%（与≥50%、1 - 49%或未知相比）以及鳞状组织学（与非鳞状相比）。在264例疾病进展的患者中，48.5%接受了后续药物治疗。单独使用ICI（9.9个月）或ICI与化疗联合（11.8个月）的中位OS-2长于铂类双联化疗（6.7个月）。对于末次度伐利尤单抗输注后＜6个月复发的患者，各治疗组的OS-2相似。
在本研究队列中，与＜65岁的患者相比，接受cCRT后使用度伐利尤单抗治疗的≥75岁患者的OS显著缩短。疾病进展后的全身治疗疗效一般，凸显了对新疗法的需求。
