Purpose. Different combination modalities between an anti-PD-1/PD-L1 agent and a platinum-based chemotherapy or another checkpoint inhibitor (with or without a short course or full course of a platinum doublet) proved superior to chemotherapy alone in multiple clinical trials, but these strategies were not directly compared. The aim of this study is to report the real-world data results with different immunotherapy combinations in a series of patients treated in consecutive cohorts at the Ion Chiricuță Oncology Institute. Methods. A total of 122 patients were successively enrolled in three cohorts: (1A) nivolumab + ipilimumab (18 patients), (1B) nivolumab + ipilimumab + short-course chemotherapy (33 patients), and (2) pembrolizumab plus full-course chemotherapy (71 patients). Endpoints included overall survival (OS), progression-free survival (PFS), objective response (ORR), and univariate and multivariate exploratory analysis of prognostic factors. RESULTS. Median follow-up in the consecutive cohorts 1A, 1B, and 2 was 83 versus 59 versus 14.2 months. Median OS and PFS for all patients were 22.2 and 11.5 months, respectively, and 2-year actuarial OS and PFS were 49% and 35%, respectively. For the nivolumab + ipilimumab (cohorts 1A and 1B) versus pembrolizumab combinations (cohort 2), median OS was 14 vs. 24.8 months (p= 0.18) and 2-year actuarial survival 42% vs. 53%; median PFS was 8.6 vs. 12.7 months (p= 0.41) and 2-year actuarial PFS 34% vs. 35%; response rates were 33.3% vs. 47.9% (p= 0.22). Older age, impaired PS (2 versus 0–1), corticotherapy in the first month of immunotherapy, and >3.81 neutrophils to lymphocytes ratio were independent unfavorable prognostic factors in the multivariate analysis of survival (limited to 2 years follow-up). The 5-year long-term survival was 30.5% and 18.8% for cohorts 1A and 1B, respectively (not enough follow-up for cohort 2). Conclusions. Efficacy results using different immunotherapy combination strategies were promising and not significantly different between protocols at 2 years. Real-world efficacy and long-term results in our series were in line with those reported in the corresponding registration trials.
目的。多项临床试验已证实，抗PD-1/PD-L1药物联合铂类化疗或另一种检查点抑制剂（联合或不联合短程或全疗程铂类双药化疗）的疗效优于单纯化疗，但这些策略尚未进行直接比较。本研究旨在报告Ion Chiricuță肿瘤研究所连续队列患者中不同免疫联合治疗方案的真实世界数据结果。方法。共122例患者连续纳入三个队列：（1A）纳武利尤单抗+伊匹木单抗（18例），（1B）纳武利尤单抗+伊匹木单抗+短程化疗（33例），以及（2）帕博利珠单抗+全疗程化疗（71例）。研究终点包括总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR），以及对预后因素进行的单变量和多变量探索性分析。结果。连续队列1A、1B和2的中位随访时间分别为83个月、59个月和14.2个月。所有患者的中位OS和PFS分别为22.2个月和11.5个月，2年精算OS率和PFS率分别为49%和35%。纳武利尤单抗+伊匹木单抗方案（队列1A和1B）与帕博利珠单抗联合方案（队列2）相比，中位OS为14个月对24.8个月（p=0.18），2年精算生存率为42%对53%；中位PFS为8.6个月对12.7个月（p=0.41），2年精算PFS率为34%对35%；缓解率分别为33.3%对47.9%（p=0.22）。在多变量生存分析（限于2年随访）中，年龄较大、体能状态较差（2分对0-1分）、免疫治疗首月使用皮质类固醇治疗以及中性粒细胞与淋巴细胞比值>3.81是独立的不良预后因素。队列1A和1B的5年长期生存率分别为30.5%和18.8%（队列2随访时间不足）。结论。采用不同免疫联合治疗策略的疗效结果令人鼓舞，且在2年时各方案间无显著差异。本系列研究的真实世界疗效和长期结果与相应注册试验报告的结果一致。
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