Elkrief Arielle, Méndez-Salazar Eder Orlando, Maillou Jade, Vanderbilt Chad M, Gogia Pooja, Desilets Antoine, Messaoudene Meriem, Kelly Daniel, Ladanyi Marc, Hellmann Matthew D, Zitvogel Laurence, Rudin Charles M, Routy Bertrand, Derosa Lisa, Schoenfeld Adam J
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
NPJ Precis Oncol. 2024 Jul 16;8(1):143. doi: 10.1038/s41698-024-00630-w.
Anti-PD(L)-1 inhibition combined with platinum doublet chemotherapy (Chemo-IO) has become the most frequently used standard of care regimen in patients with non-small cell lung cancer (NSCLC). The negative impact of antibiotics on clinical outcomes prior to anti-PD(L)-1 inhibition monotherapy (IO) has been demonstrated in multiple studies, but the impact of antibiotic exposure prior to initiation of Chemo-IO is controversial. We assessed antibiotic exposures at two time windows: within 60 days prior to therapy (-60 d window) and within 60 days prior to therapy and 42 days after therapy (-60 + 42d window) in 2028 patients with advanced NSCLC treated with Chemo-IO and IO monotherapy focusing on objective response rate (ORR: rate of partial response and complete response), progression-free survival (PFS), and overall survival (OS). We also assessed impact of antibiotic exposure in an independent cohort of 53 patients. Univariable and multivariable analyses were conducted along with a meta-analysis from similar studies. For the -60 d window, in the Chemo-IO group (N = 769), 183 (24%) patients received antibiotics. Antibiotic exposure was associated with worse ORR (27% vs 40%, p = 0.001), shorter PFS (3.9 months vs. 5.9 months, hazard ratio [HR] 1.35, 95%CI 1.1,1.6, p = 0.0012), as well as shorter OS (10 months vs. 15 months, HR 1.50, 95%CI 1.2,1.8, p = 0.00014). After adjusting for known prognostic factors in NSCLC, antibiotic exposure was independently associated with worse PFS (HR 1.39, 95%CI 1.35,1.7, p = 0.002) and OS (HR 1.61, 95%CI 1.28,2.03, p < 0.001). Similar results were obtained in the -60 + 42d window, and also in an independent cohort. In a meta-analysis of patients with NSCLC treated with Chemo-IO (N = 4) or IO monotherapy (N = 13 studies) antibiotic exposure before treatment was associated with worse OS among all patients (n = 11,351) (HR 1.93, 95% CI 1.52, 2.45) and Chemo-IO-treated patients (n = 1201) (HR 1.54, 95% CI 1.28, 1.84). Thus, antibiotics exposure prior to Chemo-IO is common and associated with worse outcomes, even after adjusting for other factors. These results highlight the need to implement antibiotic stewardship in routine oncology practice.
抗程序性死亡受体（配体）-1（PD[L]-1）抑制剂联合铂类双联化疗（化疗-免疫治疗）已成为非小细胞肺癌（NSCLC）患者最常用的标准治疗方案。多项研究已证实抗生素对单药抗PD[L]-1抑制治疗（免疫治疗）前临床结局有负面影响，但化疗-免疫治疗开始前抗生素暴露的影响存在争议。我们评估了2028例接受化疗-免疫治疗和免疫治疗单药的晚期NSCLC患者在两个时间窗口的抗生素暴露情况：治疗前60天内（-60天窗口）以及治疗前60天内和治疗后42天内（-60+42天窗口），重点关注客观缓解率（ORR：部分缓解和完全缓解率）、无进展生存期（PFS）和总生存期（OS）。我们还评估了53例独立队列患者中抗生素暴露的影响。进行了单变量和多变量分析以及来自类似研究的荟萃分析。对于-60天窗口，在化疗-免疫治疗组（N=769）中，183例（24%）患者接受了抗生素治疗。抗生素暴露与较差的ORR相关（27%对40%，p=0.001）、较短的PFS（3.9个月对5.9个月，风险比[HR]1.35，95%CI 1.1,1.6，p=0.0012）以及较短的OS（10个月对15个月，HR 1.50，95%CI 1.2,1.8，p=0.00014）。在调整NSCLC已知预后因素后，抗生素暴露与较差的PFS（HR 1.39，95%CI 1.35,1.7，p=0.002）和OS（HR 1.61，95%CI 1.28,2.03，p<0.001）独立相关。在-60+42天窗口以及独立队列中也获得了类似结果。在对接受化疗-免疫治疗（N=4）或免疫治疗单药（N=13项研究）的NSCLC患者进行的荟萃分析中，治疗前抗生素暴露与所有患者（n=11351）较差的OS相关（HR 1.93，95%CI 1.52,2.45）以及接受化疗-免疫治疗的患者（n=1201）较差的OS相关（HR 1.54，95%CI 1.28,1.84）。因此，化疗-免疫治疗前抗生素暴露很常见且与较差的结局相关，即使在调整其他因素后也是如此。这些结果凸显了在常规肿瘤学实践中实施抗生素管理的必要性。
