Supplementary Material for: Non-small cell lung cancer treated with epidermal growth factor receptor inhibitors: the effect of concurrent medications on patient outcomes

Introduction: EGFR tyrosine kinase inhibitor (TKI)-induced rash can be alleviated with tetracyclines (TCN) and topical corticosteroids (TCS), whereas drugs for acid-related disorders (DARD) can affect EGFR TKI absorption. The present study investigated the concomitant use of TCNs, TCSs, and DARDs with EGFR-TKIs in non-small cell lung cancer (NSCLC) and whether these affect patient outcomes.
Methods: We retrospectively collected data from all patients (n=1498) who had purchased for EGFR TKIs (erlotinib, gefitinib, and afatinib) in Finland between 2011-2020. Overall survival (OS) and time on treatment (ToT) were analyzed from the first EGFR TKI purchase.
Results: Early TCN purchases were registered in 298 (19.6%) patients; early TCS and DARD purchases were observed in 154 (10.1%) and 192 (12.9%) while similar percentages were detected in the EGFR mutant cohort. In the entire cohort, early purchase of TCSs and TCNs was associated with improved ToT, OS, and DARDs with inferior outcomes. In the multivariate analysis, TCSs retained their significance in ToT (HR, 0.78; 95% 0.66-0.94), TCNs in OS (HR, 0.73; 95% 0.63-0.84), and DARDs in both (HR, 1.28; 95% 1.091-1.495; HR, 1.19; 95% 1.01-1.41). In the EGFR mutant cohort, similar non-significant trends were observed for TCSs and DARDs. In the analysis according to EGFR TKI, erlotinib users had improved outcomes when early TCN or TCS purchases were registered, whereas DARDs were associated with worse outcomes among gefitinib users.
Conclusions: Among EGFR-TKI-treated NSCLCs, the use of TCN, TCS, and DARD can affect treatment outcomes that should be considered in optimal patient care.

引言：表皮生长因子受体酪氨酸激酶抑制剂（EGFR tyrosine kinase inhibitor, TKI）所致皮疹可通过四环素类（tetracyclines, TCN）与外用糖皮质激素（topical corticosteroids, TCS）缓解，而酸相关性疾病用药（drugs for acid-related disorders, DARD）会影响EGFR TKI的吸收。本研究针对非小细胞肺癌（non-small cell lung cancer, NSCLC）患者，探究其EGFR-TKI治疗期间同时使用TCN、TCS与DARD的情况，以及上述药物是否会对患者预后产生影响。
方法：本研究回顾性收集2011-2020年间芬兰地区所有购买过EGFR-TKI（厄洛替尼、吉非替尼及阿法替尼）的患者（n=1498）的临床数据。以首次购买EGFR-TKI为时间起点，分析患者的总生存期（overall survival, OS）与治疗持续时间（time on treatment, ToT）。
结果：298例（19.6%）患者存在早期TCN用药记录；早期使用TCS与DARD的患者分别为154例（10.1%）与192例（12.9%），EGFR突变亚组中也观察到了相似的占比。在全部队列中，早期使用TCS与TCN与更长的治疗持续时间、更佳的总生存期相关，而早期使用DARD则与不良预后相关。多因素分析显示，TCS对治疗持续时间仍具有显著影响（风险比HR=0.78，95%置信区间：0.66-0.94），TCN对总生存期的影响仍具有统计学意义（HR=0.73，95%置信区间：0.63-0.84），DARD则对二者均存在负面影响（HR=1.28，95%置信区间：1.091-1.495；HR=1.19，95%置信区间：1.01-1.41）。在EGFR突变亚组中，TCS与DARD仅呈现出相似的非显著性趋势。按EGFR-TKI种类分层分析显示，早期联用TCN或TCS的厄洛替尼使用者预后更佳，而吉非替尼使用者若早期联用DARD则预后更差。
结论：在接受EGFR-TKI治疗的非小细胞肺癌患者中，TCN、TCS与DARD的使用会对治疗结局产生影响，临床优化患者诊疗时应将上述因素纳入考量。