Feasibility and safety of PD-1/L1 inhibitors for non-small cell lung cancer in front-line treatment: a Bayesian network meta-analysis

Abstract

Background: This Bayesian network meta-analysis (NMA) was conducted to compare efficacy and safety of programmed death 1/ligand 1 (PD-1/L1) inhibitors in previous untreated advanced non-small cell lung cancer (NSCLC) patients.Methods: Eligible studies evaluating first-line anti-PD-1/L1 based regimens in advanced NSCLC patients were included. Overall survival (OS), progression free survival (PFS), objective response rate (ORR), as well as treatment-related severe adverse events (tr-SAE) were synthesized within the Bayesian framework.Subgroup analysis was conducted according to PD-L1 expression.Results: Twelve studies including 7,490 patients and 9 treatment strategies were enrolled in this study.For the PD-L1 expression non-selective patients, all chemo-immunotherapies were significantly better than chemotherapy for prolonging OS and PFS, except for caremlizumab plus chemotherapy (HR =0.72) failed to show advantages for OS. In addition, pembrolizumab plus chemotherapy showed better PFS than nivolumab plus ipilimumab (HR =0.66). In PD-L1 ≥50% patients, all immunotherapy was better than chemotherapy for OS, except for nivolumab (HR =0.83) and nivolumab plus ipilimumab (HR =0.70). For PFS, pembrolizumab plus chemotherapy (HR =0.39), atezolizumab plus chemotherapy (HR =0.47) and pembrolizumab (HR =0.67) were significantly better than chemotherapy. In PD-L1 1-49% patients, pembrolizumab plus chemotherapy (HR =0.52) and atezolizumab plus chemotherapy (HR =0.70) were better than chemotherapy for PFS. In the PD-L1 positive or negative group, all included corresponding regimens were equivalence according to OS and PFS. Conclusions:We conducted a systematic comparison of first line immunotherapy for advanced NSCLC. Chemo-immunotherapies were better than chemotherapy and mono-immunotherapies in most patients.Pembrolizumab might have better efficacy than other PD-1/L1 inhibitors.

Selection of optimal first-line immuno-related therapy based on specific pathological characteristics for patients with advanced driver-gene wild-type non-small cell lung cancer: a systematic review and network meta-analysis

“…Indirect comparison implied that ICI-containing treatments were significantly superior to ICI-free treatments in OS, partly consistent with conclusions of previous meta-analyses. 40 , 41 Among the 18 comparable treatments, the top 10 OS were all from ICI-based treatments, and all ICI-free treatments ranked in the bottom eight. In contrast to ICI, the current status of CT seems to be crumbling.…”

Pembrolizumab Alone or Combined With Chemotherapy in Advanced NSCLC With PD-L1 ≥50%: Results of a Retrospective Study

“…PC performed significantly better than PM in terms of ORR (OR 1.60, 95% CI 1.20-2.20), PFS (HR 0.52, 95% CI 0.37-0.71) but not for OS (HR 0.75, 95% CI 0.51-1.10) in patients with PD-L1 high expression (10). In addition, Liang et al found that PC was comparable to PM in terms of OS and PFS (HR = 1.01, 95% CI: 0.63 to 1.57 and HR = 0.59, 95% CI: 0.35 to 1.06) in patients with PD-L1 high expression by meta-analysis (7). Those results of meta-analysis were different or even opposite, which might be due to the inherent limitation such as the risk of systematic bias and confounding factors.…”

“…The mechanism of chemotherapy plus immunotherapy is not fully understood. However, there was evidence suggesting that chemotherapy can stimulate the antigenicity and immunogenicity of the host by enhancing antigen processing and presentation and by eliminating immune-suppressive myeloid derived suppressor cells (MDSC) and regulatory T cells (Tregs) (7,(23)(24)(25)(26). Meanwhile, Ramakrishnan et al proposed that chemotherapy may stimulate tumor cells to CTLs via the upregulation of mannose-6-phosphate receptors (MPRs), and autophagy may exert a tremendous influence in the immunogenic signaling during chemotherapy, which might contribute to the synergistic effect of chemotherapy and immunotherapy (23).…”

“…In addition, Liang et al. found that PC was comparable to PM in terms of OS and PFS (HR = 1.01, 95% CI: 0.63 to 1.57 and HR = 0.59, 95% CI: 0.35 to 1.06) in patients with PD-L1 high expression by meta-analysis ( 7 ). Those results of meta-analysis were different or even opposite, which might be due to the inherent limitation such as the risk of systematic bias and confounding factors.…”

“…Of note, PM has been given a high-priority rating though it is difficult to figure out which one was the best option due to the absence of direct comparison. Several meta-analyses compared the efficacy of PC and PM indirectly but presented paradoxical result, which might be due to the inherent limitation such as the risk of systematic bias and confounding factors ( 5 , 7 – 9 ). In this context, the present study aimed to figure out which therapy was the priority in this specific population by head-to-head comparison.…”