Kun Yi1, Qian Zhu2, Yu-Kang Kuang3, Si-Cong Jiang4, Hao Hu5. 1. Department of Lymphoma and Hematology, Jiangxi Cancer Hospital of Nanchang University, Nanchang, People's Republic of China. 2. Department of Intensive Care Unit, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. 3. Department of Thoracic Surgery, Jiangxi Cancer Hospital of Nanchang University, Nanchang, People's Republic of China. 4. Department of Thoracic Surgery, Jiangxi Cancer Hospital of Nanchang University, Nanchang, People's Republic of China. Electronic address: jiangsicong666@163.com. 5. Department of Radiation Therapy, General Hospital of Southern Theater Command of Chinese People's Liberation Army, Guangzhou, People's Republic of China. Electronic address: qianhe89513@163.com.
Abstract
INTRODUCTION: Programmed death receptor-1 (PD-1) and its ligand (PD-L1) inhibitors have shown promising results in treating advanced non-small-cell lung cancer (NSCLC). Our objective was to compare the relative and absolute benefits between PD-1 and PD-L1 inhibitors in advanced NSCLC. MATERIALS AND METHODS: PubMed, EMBASE and the Cochrane Library were searched up to Dec 1, 2019, for randomized controlled trials of PD-1/PD-L1 inhibitors that had available overall survival (OS) data in NSCLC. Random-effects models were used to calculate the pooled estimates. RESULTS: Twenty-three randomized controlled trials (15,797 patients) of PD-1/PD-L1 inhibitors were included in the analysis. PD-1 inhibitors significantly extended OS compared with standard of care therapy (difference in means, 4.80 months, 95% CI 3.41-6.18; HR 0.72, 95% CI 0.66-0.78; P < 0.01 for both). PD-L1 inhibitors also significantly improved OS compared with standard of care therapy (difference in means, 2.59 months 95% CI 1.47-3.71; HR 0.83, 95% CI 0.79-0.88; P < 0.01 for both). More importantly, PD-1 inhibitors had significantly higher OS than PD-L1 inhibitors (difference in means, P = 0.015; HR, P = 0.006). The same increased OS benefit was observed in patients with PD-L1 ≥1% (P = 0.035) and PD-L1 <1% (P = 0.007). However, OS did not differ between PD-1 and PD-L1 inhibitors in patients with an EGFR mutation-positive status (P = 0.724) and who were never smokers (P = 0.999). CONCLUSIONS: PD-1 inhibitors showed superior relative and absolute OS benefits compared with PD-L1 inhibitors in the treatment of advanced NSCLC. These findings have implications for treatment selection in current clinical practice and future study design.
INTRODUCTION:Programmed death receptor-1 (PD-1) and its ligand (PD-L1) inhibitors have shown promising results in treating advanced non-small-cell lung cancer (NSCLC). Our objective was to compare the relative and absolute benefits between PD-1 and PD-L1 inhibitors in advanced NSCLC. MATERIALS AND METHODS: PubMed, EMBASE and the Cochrane Library were searched up to Dec 1, 2019, for randomized controlled trials of PD-1/PD-L1 inhibitors that had available overall survival (OS) data in NSCLC. Random-effects models were used to calculate the pooled estimates. RESULTS: Twenty-three randomized controlled trials (15,797 patients) of PD-1/PD-L1 inhibitors were included in the analysis. PD-1 inhibitors significantly extended OS compared with standard of care therapy (difference in means, 4.80 months, 95% CI 3.41-6.18; HR 0.72, 95% CI 0.66-0.78; P < 0.01 for both). PD-L1 inhibitors also significantly improved OS compared with standard of care therapy (difference in means, 2.59 months 95% CI 1.47-3.71; HR 0.83, 95% CI 0.79-0.88; P < 0.01 for both). More importantly, PD-1 inhibitors had significantly higher OS than PD-L1 inhibitors (difference in means, P = 0.015; HR, P = 0.006). The same increased OS benefit was observed in patients with PD-L1 ≥1% (P = 0.035) and PD-L1 <1% (P = 0.007). However, OS did not differ between PD-1 and PD-L1 inhibitors in patients with an EGFR mutation-positive status (P = 0.724) and who were never smokers (P = 0.999). CONCLUSIONS:PD-1 inhibitors showed superior relative and absolute OS benefits compared with PD-L1 inhibitors in the treatment of advanced NSCLC. These findings have implications for treatment selection in current clinical practice and future study design.