Affiliation:
1. Department of Oncology, Xiangya Hospital, Central South University , Changsha, China
2. Xiangya Lung Cancer Center, Xiangya Hospital, Central South University , Changsha, China
3. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University , Changsha, China
Abstract
Abstract
Introduction
Programmed death 1 (PD-1)/programmed death 1 ligand 1 (PD-L1)-directed immunotherapy has revolutionized the treatments for advanced non-small cell lung cancer (NSCLC), whereas the optimal therapeutic combinations remain uncertain.
Methods
Our study encompassed phase II/III randomized controlled trials (RCTs) that involved anti-PD-(L)1-based therapies for stage-IV NSCLC. The primary outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and incidences of adverse events. Subgroup analyses were conducted by treatment lines, PD-L1 expression levels, histological types, and metastatic sites.
Results
Our analysis incorporated 38 publications, covering 14 therapeutic combinations and involving 18 048 participants. PD-(L)1+chemotherapy (CT), PD-(L)1+ cytotoxic T lymphocyte-associated antigen-4 (CTLA4) +CT, and PD-(L)1+ T-cell immunoglobulin and ITIM domain were notably effective in prolonging OS. Overall, PD-(L)1+CT and PD-(L)1+CT+ vascular endothelial growth factor (VEGF) were significantly beneficial for PFS and ORR. As for the subsequent-line treatments, incorporating radiotherapy can enhance PFS and ORR (ranked fourth among enrolled treatments). For patients with PD-L1 <1%, PD-(L)1+CT+VEGF and PD-(L)1+CTLA4+CT were favorable approaches. Conversely, in patients with PD-L1 ≥50%, PD-(L)1+CT represented an effective treatment. Patients with nonsquamous cell carcinoma or liver metastases might benefit from the addition of VEGF. In cases of squamous cell carcinoma or brain metastases, the combination of PD-(L)1+CTLA4+CT yielded superior benefits.
Conclusions
This study underscores the enhanced efficacy of combination immunotherapies over monotherapy. It highlights the necessity for personalized treatment, considering individual factors. These insights are vital for clinical decision making in the management of advanced NSCLC.
Funder
Clinical Research Special Fund of Wu Jieping Medical Foundation
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University
Publisher
Oxford University Press (OUP)