Purchase of prophylactic topical corticosteroids is associated with improved survival in NSCLCs treated with EGFR TKI: real-world cohort study

With the first- and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), clinical benefit and rash correlate together. EGFR TKI-induced rash can be alleviated with topical corticosteroids and tetracyclines. This study investigates whether prophylaxis with topical corticosteroids is associated with improved survival among the EGFR TKI-treated non-small cell lung cancers (NSCLCs). We collected all the patients (<i>n</i> = 1271) who had received reimbursement for the first- or second-generation EGFR TKIs in Finland 2011–2016, had purchased TKIs, and had data available at the Finnish Cancer Registry (FCR). Survival was analyzed from the first EGFR TKI purchase to death or the end of follow-up, and patients were stratified according to the TKIs, purchases of topical corticosteroids, and their timing. A total of 270 (21%) patients had corticosteroid purchases −14 to +200 d (all), and 196 (15%) had purchased corticosteroids as prophylaxis (−14 to +14 d) from the first EGFR TKI purchase. Corticosteroid purchases were associated with improved survival in all (0.64 95% CI 0.56–0.74) and prophylactic (0.78, 95% CI 0.66–0.92) groups when compared to non-purchasers, although these results were limited to the erlotinib users only. The survival benefit of prophylactic corticosteroids among the erlotinib users remained in multivariate analysis including sex, stage, histology, and tetracycline prophylaxis (HR 0.78, 95% CI 0.64–0.95). The prophylactic use of corticosteroids was associated with a longer erlotinib treatment duration (HR 0.75, 95% CI 0.64–0.90). Prophylactic topical corticosteroids may improve the survival of NSCLC patients treated with EGFR TKIs, and they should be considered as prophylaxis when initiating EGFR TKIs with a high incidence of rash.

第一代和第二代表皮生长因子受体（epidermal growth factor receptor, EGFR）酪氨酸激酶抑制剂（tyrosine kinase inhibitors, TKIs）的临床获益与皮疹具有相关性。EGFR TKI诱导的皮疹可通过外用糖皮质激素与四环素类药物缓解。本研究旨在探讨外用糖皮质激素预防治疗是否可改善接受EGFR TKI治疗的非小细胞肺癌（non-small cell lung cancer, NSCLC）患者的生存结局。我们收集了2011–2016年在芬兰获批第一代或第二代EGFR TKI报销、已购买该类药物且在芬兰癌症登记处（Finnish Cancer Registry, FCR）存有相关数据的全部患者（n=1271）。生存分析以首次购买EGFR TKI为起始时间，至患者死亡或随访结束为截尾时间，并根据患者使用的TKI种类、是否购买外用糖皮质激素及其用药时机进行分层。共计270例（21%）患者在首次EGFR TKI购买后的-14至+200天内购买了糖皮质激素，其中196例（15%）在首次EGFR TKI购买后的-14至+14天内购买糖皮质激素以作为预防治疗。与未购买糖皮质激素的患者相比，所有糖皮质激素购买者（风险比（hazard ratio, HR）0.64，95%置信区间（confidence interval, CI）0.56–0.74）与预防性糖皮质激素使用者（风险比（hazard ratio, HR）0.78，95%置信区间（confidence interval, CI）0.66–0.92）的生存结局均得到改善，但上述结果仅在使用厄洛替尼（erlotinib）的患者亚组中显著。在纳入性别、肿瘤分期、组织学类型与四环素类药物预防治疗的多变量回归分析中，厄洛替尼使用者接受预防性糖皮质激素的生存获益仍具有统计学意义（风险比（hazard ratio, HR）0.78，95%置信区间（confidence interval, CI）0.64–0.95）。预防性外用糖皮质激素还与更长的厄洛替尼治疗持续时间相关（风险比（hazard ratio, HR）0.75，95%置信区间（confidence interval, CI）0.64–0.90）。综上，预防性外用糖皮质激素或可改善接受EGFR TKI治疗的NSCLC患者的生存结局，对于皮疹发生率较高的EGFR TKI治疗方案，临床应考虑将其作为预防用药。