背景:在一项针对IIIB/IV期非鳞状非小细胞肺癌(NSCLC)患者的开放标签多中心非随机非比较II期研究中,致癌成瘾(EGFR突变或ALK/ROS1融合),酪氨酸激酶抑制剂后的疾病进展和没有先前的化疗(NCT04042558),阿替珠单抗,卡铂,培美曲塞联合或不联合贝伐单抗显示出一些有希望的结果.除了临床评估,我们评估了安全性和患者报告结局(PRO),以提供额外信息,说明在该人群中,在有和没有贝伐单抗的情况下,在化疗中添加阿特珠单抗的相对影响.
方法:患者接受铂-培美曲塞-阿替珠单抗-贝伐单抗(PPAB队列)或,如果不符合资格,铂-培美曲塞-阿替珠单抗(PPA队列)。发病率,自然,并评估不良事件(AE)的严重程度。使用欧洲癌症研究和治疗组织生活质量问卷(EORTCQLQ-Core30和EORTCQLQ-肺癌13)评估PRO。
结果:总体而言,68例(PPAB)和72例(PPA)患者的安全性可评估。3-4级不良事件发生率为83.8%(PPAB)和63.9%(PPA)。3-4级阿替珠单抗相关的不良事件发生率分别为29.4%和19.4%,分别。3-4级贝伐单抗相关AE发生率为36.8%(PPAB)。最常见的3-4级AE是中性粒细胞减少症(PPAB中为19.1%;PPA中为23.6%)和虚弱症(PPAB中为16.2%;PPA中为9.7%)。在PPAB中,我们观察到全球卫生安全(GHS)评分的全球稳定性,疲劳和呼吸困难不断改善的趋势,咳嗽有显著改善.在PPA中,我们观察到GHS评分显着改善,疲劳显着改善,呼吸困难和咳嗽。在第54周,我们观察到49.2%的患者的GHS评分相对于基线有所改善。在这两个队列中,患者的总体健康或身体功能评分平均无临床显著恶化.
结论:PPAB和PPA联合治疗在具有致癌成瘾(EGFR突变或ALK/ROS1融合)的IIIB/IV期非鳞NSCLC患者中,在靶向治疗后似乎是可以耐受和控制的。
BACKGROUND: In an open-label multicenter non-randomized non-comparative phase II study in patients with stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC), oncogenic addiction (EGFR mutation or ALK/ROS1 fusion), with disease progression after tyrosine-kinase inhibitor and no prior chemotherapy (NCT04042558), atezolizumab, carboplatin, pemetrexed with or without bevacizumab showed some promising result. Beyond the clinical evaluation, we assessed safety and patient-reported outcomes (PROs) to provide additional information on the relative impact of adding atezolizumab to chemotherapy with and without bevacizumab in this population.
METHODS: Patients received platinum-pemetrexed-atezolizumab-bevacizumab (PPAB cohort) or, if not eligible, platinum-pemetrexed-atezolizumab (PPA cohort). The incidence, nature, and severity of adverse events (AEs) were assessed. PROs were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-Core 30 and EORTC QLQ-Lung Cancer 13).
RESULTS: Overall, 68 (PPAB) and 72 (PPA) patients were evaluable for safety. Grade 3-4 AEs occurred in 83.8% (PPAB) and 63.9% (PPA). Grade 3-4 atezolizumab-related AEs occurred in 29.4% and 19.4%, respectively. Grade 3-4 bevacizumab-related AEs occurred in 36.8% (PPAB). Most frequent grade 3-4 AEs were neutropenia (19.1% in PPAB; 23.6% in PPA) and asthenia (16.2% in PPAB; 9.7% in PPA). In PPAB, we observed a global stability in global health security (GHS) score, fatigue and dyspnea with a constant tendency of improvement, and a significant improvement in cough. In PPA, we observed a significant improvement in GHS score with a significant improvement in fatigue, dyspnea and cough. At week 54, we observed an improvement from baseline in GHS score for 49.2% of patients. In both cohorts, patients reported on average no clinically significant worsening in their overall health or physical functioning scores.
CONCLUSIONS: PPAB and PPA combinations seem tolerable and manageable in patients with stage IIIB/IV non-squamous NSCLC with oncogenic addiction (EGFR mutation or ALK/ROS1 fusion) after targeted therapies.