Association of PD‐L1 expression status with the efficacy of PD‐1/PD‐L1 inhibitors and overall survival in solid tumours: A systematic review and meta‐analysis
| Autor: | Fang-Fang Tou, Xiao-Ming Wen, Hao Hu, Xi Liu, Qian Zhu, Yu-Kang Kuang, Chang-Ying Guo |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Durvalumab Programmed Cell Death 1 Receptor Pembrolizumab Cochrane Library B7-H1 Antigen Avelumab 03 medical and health sciences Antineoplastic Agents Immunological 0302 clinical medicine Atezolizumab Neoplasms Internal medicine Humans Medicine Immune Checkpoint Inhibitors Randomized Controlled Trials as Topic business.industry Hazard ratio Survival Rate 030220 oncology & carcinogenesis Meta-analysis Nivolumab business medicine.drug |
| Zdroj: | International Journal of Cancer. 147:116-127 |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.32744 |
| Popis: | Whether PD-L1-positive patients derive more overall survival benefit from PD-1/PD-L1 inhibitors in the treatment of advanced solid tumours is unclear. We systematically searched the PubMed, Cochrane library and EMBASE databases from January 1, 1966 to March 1, 2019, to identify randomised controlled trials of PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, atezolizumab, durvalumab and avelumab) that had available hazard ratios (HRs) for death according to PD-L1 status. A random-effects model was used to calculate the pooled overall survival (OS) HR and 95% CI among PD-L1-positive and PD-L1-negative patients. An interaction test was performed to evaluate the heterogeneity between the two estimates. A total of 24 randomised trials, involving 12,966 participants, fulfilled the inclusion criteria. An OS benefit of PD-1/PD-L1 inhibitors was found in both PD-L1-positive patients (HR, 0.65; 95% CI, 0.60-0.70) and PD-L1-negative patients (HR, 0.82; 95% CI, 0.74-0.91) even at the minimum cut-off value of 1%. Significant differences in the efficacy of PD-1/PD-L1 inhibitors between PD-L1-positive and PD-L1-negative patients were noted at different cut-off values. Moreover, there was a positive dose-response relationship between PD-L1 positivity and OS benefit (HR for 1%, 0.58, [0.50, 0.67]; 5%, 0.52 [0.43, 0.64]; 10%, 0.50 [0.40, 0.63]). Subgroup analyses showed that these results were generally consistent, regardless of study design, line of treatment, treatment type, tumour type, PD-L1 staining cell type and median follow-up time. We demonstrated that PD-1/PD-L1 inhibitors significantly improved OS in both PD-L1 positive and PD-L1 negative patients compared to controls, but the magnitude of benefit was clinically PD-L1-dependent. |
| Databáze: | OpenAIRE |
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