Introduction: Immune checkpoint blockers have revolutionized the first-line treatment of advanced non-small-cell lung cancer (NSCLC). Pembrolizumab, an anti-PD-1 monoclonal antibody, is a standard therapy either alone or in combination with chemotherapy (chemo-IO). The current study explores the efficacy and safety of pembrolizumab with carboplatin and weekly paclitaxel in a cohort of frail patients. Methods: A monocentric retrospective study was conducted between 22 September 2020 and 19 January 2023 regarding patients with stage IV NSCLC treated with chemo-IO combination: carboplatin (AUC 5 mg/mL/min; Q4W), weekly paclitaxel (90 mg/m2on days 1, 8, and 15), and pembrolizumab (200 mg Q4W). The primary objective was real-world progression-free survival (rwPFS). Secondary objectives were overall survival (OS), toxicity profile, and outcomes based on histological subtype. Results: A total of 34 patients (20 squamous and 14 non-squamous NSCLC) benefited from the chemo-IO regimen for frail patients; 41.9% had an ECOG-PS = 2. The median age was 75.5 years. We observed an overall response rate (ORR) of 55.9%. Notably, squamous NSCLC exhibited a significantly higher ORR (80%) than non-squamous NSCLC (21.4%);p= 0.001. The median rw-PFS was 10.6 months (95% CI [6.0, NA]), with 6- and 12-month rw-PFS rates of 69% and 45.8%, respectively. The median OS was not reached, with 12- and 18-month OS rates of 75.6% and 61.4%, respectively. The median number of maintenance cycles of pembrolizumab was 5 (0; 27). Nine patients (26.5%) experienced a toxicity related to chemotherapy leading to a reduction of the dose administered and, in five patients (14.7%), to the permanent discontinuation of chemotherapy. Six patients (17.6%) had an immune-related adverse event leading to the discontinuation of immunotherapy. Discussion: Pembrolizumab plus carboplatin and weekly paclitaxel demonstrates promising efficacy and safety in frail patients with metastatic NSCLC, especially for ORR in sq-NSCLC. Prospective studies focusing on frail populations are warranted in order to validate these findings and optimize therapeutic strategies in the first-line setting.
引言：免疫检查点抑制剂已彻底改变晚期非小细胞肺癌（NSCLC）的一线治疗格局。帕博利珠单抗作为一种抗PD-1单克隆抗体，已成为单药或联合化疗（免疫化疗）的标准治疗方案。本研究旨在评估帕博利珠单抗联合卡铂及周疗紫杉醇方案在体能状态脆弱患者群体中的疗效与安全性。方法：本研究为单中心回顾性分析，纳入2020年9月22日至2023年1月19日期间接受免疫化疗方案治疗的IV期NSCLC患者，治疗方案包括：卡铂（AUC 5 mg/mL/min，每4周一次）、周疗紫杉醇（第1、8、15天给药，剂量90 mg/m²）及帕博利珠单抗（200 mg，每4周一次）。主要研究终点为真实世界无进展生存期（rwPFS），次要终点包括总生存期（OS）、毒性特征及基于组织学亚型的疗效差异。结果：共34例患者（20例鳞状NSCLC，14例非鳞状NSCLC）接受了针对脆弱患者的免疫化疗方案，其中41.9%患者ECOG-PS评分为2分。中位年龄75.5岁。总体客观缓解率（ORR）达55.9%，值得注意的是鳞状NSCLC患者的ORR（80%）显著高于非鳞状NSCLC患者（21.4%）（p=0.001）。中位rwPFS为10.6个月（95% CI [6.0, NA]），6个月和12个月rwPFS率分别为69%和45.8%。中位OS尚未达到，12个月和18个月OS率分别为75.6%和61.4%。帕博利珠单抗维持治疗中位周期数为5次（范围0-27次）。9例患者（26.5%）出现化疗相关毒性反应需降低剂量，其中5例（14.7%）因此永久停用化疗。6例患者（17.6%）发生免疫相关不良事件导致免疫治疗中止。讨论：帕博利珠单抗联合卡铂及周疗紫杉醇方案在转移性NSCLC脆弱患者中展现出良好的疗效与安全性，尤其在鳞状NSCLC的客观缓解率方面表现突出。未来需开展针对脆弱人群的前瞻性研究以验证本发现，并优化一线治疗策略。
肿瘤(癌症)患者之家