Geum Min Jung, Kim Chungsoo, Kang Ji Eun, Choi Jae Hee, Kim Jae Song, Son Eun Sun, Lim Sun Min, Rhie Sandy Jeong
The Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Korea.
Department of Pharmacy, Severance Hospital, Yonsei University Health System, Seoul 03722, Korea.
Pharmaceuticals (Basel). 2021 May 8;14(5):445. doi: 10.3390/ph14050445.
Antibiotic-induced dysbiosis may affect the efficacy of immune checkpoint inhibitors. We investigated the impact of antibiotics on the clinical outcomes of nivolumab in patients with non-small cell lung cancer (NSCLC). Patients who received nivolumab for NSCLC between July 2015 and June 2018 and who were followed up until June 2020 were included in a retrospective cohort analysis. Of 140 eligible patients, 70 were on antibiotics. Overall survival (OS) was shorter in patients on antibiotics (ABX) compared to those not on antibiotics (NoABX) ( = 0.014). OS was negatively associated with piperacillin/tazobactam (PTZ) (HR = 3.31, 95% CI: 1.77-6.18), days of therapy (DOT) ≥ 2 weeks (HR = 2.56, 95% CI: 1.30-5.22) and DOT of PTZ. The defined daily dose (DDD) in PTZ (r = 0.27) and glycopeptides (r = 0.21) showed weak correlations with mortality. There was no difference in progression-free survival (PFS) between ABX and NoABX; however, PFS was negatively associated with the antibiotic class PTZ and DOT of PTZ. Therefore, the use of a broad-spectrum antibiotic, such as PTZ, the long-term use of antibiotics more than 2 weeks in total and the large amount of defined daily dose of specific antibiotics were associated with decreased survival in patients receiving nivolumab for NSCLC.
抗生素诱导的菌群失调可能会影响免疫检查点抑制剂的疗效。我们调查了抗生素对非小细胞肺癌(NSCLC)患者使用纳武单抗临床结局的影响。对2015年7月至2018年6月期间接受纳武单抗治疗NSCLC且随访至2020年6月的患者进行回顾性队列分析。140例符合条件的患者中,70例正在使用抗生素。与未使用抗生素的患者相比,使用抗生素的患者总生存期(OS)更短(P = 0.014)。OS与哌拉西林/他唑巴坦(PTZ)呈负相关(HR = 3.31,95%CI:1.77 - 6.18)、治疗天数(DOT)≥2周(HR = 2.56,95%CI:1.30 - 5.22)以及PTZ的DOT。PTZ(r = 0.27)和糖肽类(r = 0.21)的限定日剂量(DDD)与死亡率呈弱相关。ABX组和NoABX组的无进展生存期(PFS)无差异;然而,PFS与抗生素类别PTZ以及PTZ的DOT呈负相关。因此,使用广谱抗生素如PTZ、抗生素总使用时间超过2周以及特定抗生素的大量限定日剂量与接受纳武单抗治疗NSCLC患者的生存率降低相关。