Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
Medical Oncology Unit, University Hospital of Parma, Parma, Italy; Department of Medicine and Surgery, University of Parma, Parma, Italy.
Eur J Cancer. 2021 Jan;142:18-28. doi: 10.1016/j.ejca.2020.09.033. Epub 2020 Nov 16.
Concomitant medications are known to impact on clinical outcomes of patients treated with immune checkpoint inhibitors (ICIs). We aimed weighing the role of different concomitant baseline medications to create a drug-based prognostic score.
We evaluated concomitant baseline medications at immunotherapy initiation for their impact on objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in a single-institution cohort of patients with advanced cancer treated with ICIs (training cohort, N = 217), and a drug-based prognostic score with the drugs resulting significantly impacting the OS was computed. Secondly, we externally validated the score in a large multicenter external cohort (n = 1012).
In the training cohort (n = 217), the median age was 69 years (range: 32-89), and the primary tumours were non-small-cell lung cancer (70%), melanoma (14.7%), renal cell carcinoma (9.2%) and others (6%). Among baseline medications, corticosteroids (hazard ratio [HR] = 2.3; 95% confidence interval [CI]: 1.60-3.30), systemic antibiotics (HR = 2.07; 95% CI: 1.31-3.25) and proton-pump inhibitors (PPIs) (HR = 1.57; 95% CI: 1.13-2.18) were significantly associated with OS. The prognostic score was calculated using these three drug classes, defining good, intermediate and poor prognosis patients. Within the training cohort, OS (p < 0.0001), PFS (p < 0.0001) and ORR (p = 0.0297) were significantly distinguished by the score stratification. The prognostic value of the score was also demonstrated in terms of OS (p < 0.0001), PFS (p < 0.0001) and ORR (p = 0.0006) within the external cohort.
Cumulative exposure to corticosteroids, antibiotics and PPIs (three likely microbiota-modulating drugs) leads to progressively worse outcomes after ICI therapy. We propose a simple score that can help stratifying patients in routine practice and clinical trials of ICIs.
已知伴随药物会影响接受免疫检查点抑制剂 (ICI) 治疗的患者的临床结局。我们旨在权衡不同伴随基线药物的作用，以创建基于药物的预后评分。
我们评估了单机构接受 ICI 治疗的晚期癌症患者免疫治疗起始时的伴随基线药物对客观缓解率 (ORR)、无进展生存期 (PFS) 和总生存期 (OS) 的影响（训练队列，N=217），并计算了对 OS 有显著影响的药物的基于药物的预后评分。其次，我们在一个大型多中心外部队列（n=1012）中对该评分进行了外部验证。
在训练队列（n=217）中，中位年龄为 69 岁（范围：32-89），主要肿瘤为非小细胞肺癌 (70%)、黑色素瘤 (14.7%)、肾细胞癌 (9.2%) 和其他肿瘤 (6%)。在基线药物中，皮质类固醇 (HR=2.3；95%置信区间 [CI]：1.60-3.30)、全身抗生素 (HR=2.07；95%CI：1.31-3.25) 和质子泵抑制剂 (PPIs) (HR=1.57；95%CI：1.13-2.18) 与 OS 显著相关。该评分使用这三种药物类别计算，定义为预后良好、中等和不良的患者。在训练队列中，OS（p<0.0001）、PFS（p<0.0001）和 ORR（p=0.0297）通过评分分层显著区分。该评分的预后价值也在外部队列的 OS（p<0.0001）、PFS（p<0.0001）和 ORR（p=0.0006）方面得到了证明。
皮质类固醇、抗生素和 PPIs（三种可能调节肠道菌群的药物）的累积暴露导致 ICI 治疗后结局逐渐恶化。我们提出了一种简单的评分，可以帮助在 ICI 治疗的常规实践和临床试验中对患者进行分层。
