Logan Jessica M, Brooks Doug A, Rowland Andrew, Sorich Michael J, Hopkins Ashley M
Clinical and Health Sciences, Cancer Research Institute, University of South Australia, North Terrace, Adelaide 5001, South Australia, Australia.
College of Medicine and Public Health, Flinders University, Flinders Drive, Bedford Park, Adelaide 5042, South Australia, Australia.
J Oncol. 2021 Jun 16;2021:2414897. doi: 10.1155/2021/2414897. eCollection 2021.
Afatinib is a first-line treatment option for patients with an advanced nonsmall cell lung cancer (NSCLC) expressing an epidermal growth factor receptor (EGFR) activating mutation. This study aimed to evaluate the association between early adverse events induced by afatinib and overall survival (OS) and progression free survival (PFS) in patients with advanced NSCLC.
The study was a pooled post hoc analysis of the randomized trials LUX-Lung 3 and LUX-Lung 6 which evaluated afatinib versus pemetrexed-cisplatin or gemcitabine-cisplatin, respectively. Cox proportional hazard analysis was used to assess the impact of adverse events occurring within the first 28 days of afatinib therapy on the PFS and OS outcomes in treatment-naïve advanced NSCLC patients harbouring an EGFR activating mutation.
There were 468 patients who initiated first-line afatinib therapy within LUX-Lung 3 and LUX-Lung 6. A significant association between early rash and improved OS (hazard ratio (HR 95% CI); grade 1 = 0.74 [0.56-0.97]; grade 2+ = 0.64 [0.46-0.89]) ( = 0.018) was observed, although no significant association with PFS was present ( = 0.732). A significant association was identified between early diarrhoea and improved PFS (grade 1 = 0.83 [0.62-1.12]; grade 2+ = 0.62 [0.44-0.88]) ( = 0. 015), although no significant association with OS was present ( = 0.605). No associations between early stomatitis or paronychia and OS or PFS were identified.
Rash occurring early after the initiation of afatinib was significantly associated with improved OS, an indicator that rash may be a surrogate of patients likely to achieve long-term survival. Consideration of using rash as a dose adjustment target may be warranted for future prospective trials aiming to optimise outcomes with afatinib therapy.
阿法替尼是表皮生长因子受体（EGFR）激活突变的晚期非小细胞肺癌（NSCLC）患者的一线治疗选择。本研究旨在评估阿法替尼诱导的早期不良事件与晚期NSCLC患者总生存期（OS）和无进展生存期（PFS）之间的关联。
本研究是对随机试验LUX-Lung 3和LUX-Lung 6进行的汇总事后分析，这两项试验分别评估了阿法替尼与培美曲塞-顺铂或吉西他滨-顺铂的疗效。采用Cox比例风险分析评估阿法替尼治疗前28天内发生的不良事件对初治的携带EGFR激活突变的晚期NSCLC患者的PFS和OS结局的影响。
在LUX-Lung 3和LUX-Lung 6中有468例患者开始一线阿法替尼治疗。观察到早期皮疹与改善的OS之间存在显著关联（风险比（HR 95%CI）；1级=0.74[0.56-0.97]；2级及以上=0.64[0.46-0.89]）（P=0.018），尽管与PFS无显著关联（P=0.732）。早期腹泻与改善的PFS之间存在显著关联（1级=0.83[0.62-1.12]；2级及以上=0.62[0.44-0.88]）（P=0.015），尽管与OS无显著关联（P=0.605）。未发现早期口腔炎或甲沟炎与OS或PFS之间存在关联。
阿法替尼治疗后早期出现的皮疹与改善的OS显著相关，这表明皮疹可能是患者可能实现长期生存的一个替代指标。对于旨在通过阿法替尼治疗优化结局的未来前瞻性试验，考虑将皮疹作为剂量调整靶点可能是有必要的。
