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

Abstract

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 followup 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.Additional Supporting Information may be found in the online version of this article.

Case Report: Low-Dose Decitabine Plus Anti-PD-1 Inhibitor Camrelizumab for Previously Treated Advanced Metastatic Non-Small Cell Lung Cancer

“…Numerous studies have shown that PD-L1 positive patients can benefit from PD-1 or PD-L1 blockade (18,19). However, recent meta-analyses have confirmed that irrespective of whether PD-L1 is negative or positive, it can benefit from PD-1 or PD-L1 blocking antibodies (20,21). Of the three cases we studied, two were PD-L1 positive and benefited from HMAs combined with PD-1/PD-L1 antibody therapy.…”

Basis of PD1/PD-L1 Therapies

“…PD-L1 is abundantly expressed on various cancer cells [51,52] and has been extensively summarized in various reviews [13,53]. The discrepancy of some results might be due to inadequate sampling of the tumor and insufficient sensitivity of the detection method/antibody used for immunohistochemistry (IHC).…”

Prognostic and Clinicopathological Value of Programmed Cell Death Ligand1 Expression in Patients With Small Cell Lung Cancer: A Meta-Analysis

“…In a recent meta-analysis (37,38), evidence showed that PD-1/PD-L1 inhibitors significantly improve OS in patients with either PD-L1 positivity or PD-L1 negativity compared with controls (37,38). However, in these meta-analyses (37,38), patients with SCLC were not included; therefore, further studies should be conducted to investigate the impact of PD-L1 expression on the prognosis of patients with SCLC receiving ICIs. Although we performed this meta-analysis based on the PRISMA guidelines, several limitations must be acknowledged.…”

“…Notably, in the current meta-analysis, all included studies did not enroll patients receiving ICIs; therefore, whether PD-L1 expression is associated with the efficacy of ICIs and OS in patients with SCLC remains unclear. In a recent meta-analysis ( 37 , 38 ), evidence showed that PD-1/PD-L1 inhibitors significantly improve OS in patients with either PD-L1 positivity or PD-L1 negativity compared with controls ( 37 , 38 ). However, in these meta-analyses ( 37 , 38 ), patients with SCLC were not included; therefore, further studies should be conducted to investigate the impact of PD-L1 expression on the prognosis of patients with SCLC receiving ICIs.…”

“…Third, all the included studies were of a retrospective study design. Although we did not limit the study design (prospective or retrospective) in the inclusion and exclusion criteria, and we also checked relevant prospective trials ( 40 , 41 ) and meta-analyses ( 37 , 38 ), we failed to identify prospective studies in our meta-analysis because of insufficient data in those studies. We suggest that the prognostic value of PD-L1 expression in SCLC should be explored in prospective trials.…”