Due to the increasing number of trials with immune checkpoint inhibitors (ICI) in first line therapy of non–small cell lung cancer (NSCLC), we performed a systematic review and meta-analyses about the differences between anti PD-1 and PD-L1 in naïve-treatment NSCLC patients through adjusted indirect analysis to minimize the potential bias regarding overall survival (OS), progression free survival (PFS), overall response rate (ORR) and grade 3-5 adverse event (AE).
We included studies published until May 30 2020. Applicable terms, such as “lung cancer AND first line AND immunotherapy OR PD-1 OR PL-D1,” were used. Primary outcomes were OS, PFS, ORR and grade 3-5 AE. We used the random-effects model to generate pooled estimates for proportions. Meta-analyses using pooled risk ratios were performed for binary outcomes from comparative studies with the random effect model. As there are no studies with direct analyzes between PD-1 and PD-L1 treatments, we carry out indirect data analyzes using the Excel spreadsheet. All analyses were performed by REVMAN version 5.0.
Thirteen studies met our eligibility criteria, including 7673 patients (4077 cases in experimental and 3596 cases in control group). Six trials investigated ICI in monotherapy (four of them with anti-PD-1 and three with anti-PD-L1) and seven trials investigated ICI-chemotherapy combination; three used Pembrolizumabe and four used Atezolizumabe. Related to prognosis, in the ICI-chemotherapy combination group, anti-PD-1 were associated with better OS (P=0.02) and PFS (P=0.03) compared to anti-PD-L1. In monotherapy, there was no statistical difference between the use of anti-PD-1 and anti-PD-L1 for OS and PFS. Regarding ORR and toxicity, in the ICI-chemotherapy combination group, anti-PD-1 was associated with a trand better ORR (p=0.12) and less frequent grade 3-5 AE compared to the use of anti-PD-L1. In monotherapy, no statistical difference between the use of anti-PD-1 and anti-PD-L1 was observed.
Our study suggests that the combination of anti-PD-1 and chemotherapy is superior to anti-PD-L1 + chemotherapy in 1st line NSCLC therapy; in monotherapy both strategies appear to be similar.
The authors.
Has not received any funding.
All authors have declared no conflicts of interest.