PD-(L)1 inhibitors vs. chemotherapy vs. their combination in front-line treatment for NSCLC: An indirect comparison.
We comprehensively compared the therapeutic effects and safety of PD-1/L1 antibodies (I), chemotherapy (C) or their combination (I + C) as first-line treatments for advanced NSCLC. Online databases were searched to identify RCTs. Survival outcomes and safety events were pooled by indirect treatment comparison. Main subgroup analyses were conducted according to PD-L1 expression. A total of 11 RCTs involving 6,731 patients were included. Overall, PD-1/L1 inhibitors showed no difference to chemotherapy in PFS (HR 0.90, 0.65-1.24) and OS (HR 0.84, 0.64-1.09), while I + C was superior to chemotherapy both in PFS (HR 0.64, 0.58-0.71) and OS (HR 0.74, 0.62-0.89). I + C also showed advantages over PD-1/L1 in PFS (HR 0.71, 0.51-0.99) but not OS (HR 0.88, 0.64-1.22). In the PD-L1 < 1% subgroup, I + C was beneficial both in OS (HR 0.78, 0.67-0.90) and PFS (HR 0.72, 0.65-0.80) than chemotherapy. In PD-L1 ≥ 50% population, PD-1/L1 had longer OS than chemotherapy (HR 0.71, 0.60-0.84); I + C also had longer OS (HR 0.61, 0.49-0.77) and PFS (HR 0.41,0.34-0.49) than chemotherapy. In indirect analysis (PD-L1 ≥ 50%), I + C was superior to PD-1/L1 in terms of PFS (HR 0.54, 0.35-0.82), but not OS (HR 0.86, 0.65-1.14). Both treatment-related and immune-mediated adverse events occurred most frequently in the combination therapy group. We suggest that a combination regimen is preferable as first-line treatment for NSCLC patients with different PD-L1 expression, in the meanwhile, in cautious of side effects.
['Liang|Hengrui|H|', 'Liu|Zhichao|Z|', 'Cai|Xiuyu|X|', 'Pan|Zhenkui|Z|', 'Chen|Difei|D|', 'Li|Caichen|C|', 'Chen|Yingying|Y|', 'He|Jianxing|J|0000-0003-1737-8192', 'Liang|Wenhua|W|']
D000970:Antineoplastic Agents D000074322:Antineoplastic Agents, Immunological D060890:B7-H1 Antigen D002289:Carcinoma, Non-Small-Cell Lung D004358:Drug Therapy D005260:Female D006801:Humans D007167:Immunotherapy D008175:Lung Neoplasms D008297:Male D016032:Randomized Controlled Trials as Topic D016896:Treatment Outcome
chemotherapy NSCLC PD-1/L1 inhibitors