Comparison of Efficacy and Safety of Single and Double Immune Checkpoint Inhibitor-Based First-Line Treatments for Advanced Driver-Gene Wild-Type Non-Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis.
Immune checkpoint inhibitors (ICIs) have improved survival for advanced wild-type non-small cell lung cancer (NSCLC) significantly, but few studies compared single ICI (SICI)-based treatments and double ICIs (DICI)-based treatments. We summarized the general efficacy of ICI-related treatments, compared the efficacy and safety of SICI-based [programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) or cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors ± chemotherapy (CT)] and DICI-based (PD-1/PD-L1 inhibitors+CTLA-4 inhibitors ± chemotherapy) treatments vs. CT in the first-line treatment.
We included phase II/III randomized controlled trials (RCTs), including patients with histologically confirmed stage IIIB-IV driver-gene wild-type NSCLC who received first-line ICI-related therapy in at least one arm. PubMed, Embase, and Cochrane Library were searched from January 1, 2005, to December 31, 2020. This network meta-analysis was performed in a Bayesian framework using GEMTC and JAGS package in R.3.6.1. The research was registered with PROSPERO (CRD42020184534).
Twenty RCTs were involved, including 13,032 patients and 17 treatment regimens. The results showed that ICI-based therapies could provide a pooled median overall survival (mOS) (POS) of 15.79 (95% CI: 14.85-16.73) months, and there were no significant differences in OS, progression-free survival (PFS), objective response rate (ORR), and grade 3 or higher adverse events (≥3AEs) between DICI-based treatments (POS: 14.81, 12.11-17.52 months) and SICI-based treatments (POS: 16.17, 14.59-17.74 months) in overall patients. However, DICI-based treatments had significantly prolonged the OS over SICI-based treatments in squamous and PD-L1 <1% subgroups. The ranking of OS benefit by Bayesian surface under the cumulative ranking curve (SUCRA) spectrum showed that DICI+chemotherapy ranked first for overall population and subgroups including squamous, non-squamous, any level of PD-L1 expression, smoking, male, Eastern Cooperative Oncology Group performance status (ECOG PS) = 0/1, age < 65/≥65 while SICI+CT for low tumor mutation burden (TMB), non-smoking, and female subgroups, and DICI for high TMB subgroups.
In the first-line therapy for advanced wild-type NSCLC, both SICI- and DICI-based treatments could bring significant overall advantages over chemotherapy, with comparable outcomes of efficacy and ≥3AEs. DICI-based treatments were more effective than SICI-based treatments in squamous and PD-L1 <1% subgroups. For most populations, DICI+chemotherapy could be the best choice with a survival benefit, while SICI+chemotherapy has established its position actually.
[PROSPERO], identifier [CRD42020184534].
Xu Q
，Zhang X
，Huang M
，Dai X
，Gao J
，Li S
，Sheng L
，Huang K
，Wang J
，Liu L
... -
《Frontiers in Immunology》
Anti-PD-1 and Anti-PD-L1 in Head and Neck Cancer: A Network Meta-Analysis.
The monoclonal antibodies anti-programmed death protein-1 (anti-PD-1) nivolumab and pembrolizumab are the first immune checkpoint inhibitors (ICIs) approved for treatment of recurrent/metastatic head and neck carcinoma R/M HNSCC in first line and in platinum refractory disease. This network meta-analysis aims to investigate the efficacy of anti-PD-1- vs anti-PD-L1-based therapy in R/M HNSCC cancer patients through a systematic review of the literature to provide support for evidence-based treatment decisions. In particular, the effectiveness of ICIs for R/M HNSCC is analyzed according to the different mechanisms of action of the check-points inhibitory drugs in different subgroups of patients.
We did a systematic literature review and network meta-analysis (NMA) of randomized controlled trials (RCTs) in PubMed, ClinicalTrials.gov, Embase, Medline, the Cochrane Central Register of Controlled Trials, Web of Science. Our search identified a total of five randomized controlled trials: Keynote 040, Keynote 048, Eagle, Condor, Checkmate 141. These trials included 3001 patients. Treatment was sub-categorized into PD-L1-based, PD-1-based, and standard chemotherapy. Treatments were indirectly compared with anti-PD-L1-based therapy.
The network meta-analysis demonstrated no significant differences in OS between different subgroups except for the metastatic patients in which anti-PD-1-based therapy was associated with significantly less risk of death. Furthermore, anti-PD-1-based therapy appeared to be effective in smoker patients and in human papilloma-negative (HPV) patients. Conversely, anti-PD-L1-based therapy seems to be better efficient in female patients, in locally recurrent setting and in HPV positive patients.
This is the first NMA study that aimed to indirectly compare anti-PD-1- and anti-PD-L1-based therapy in HNSCC patients. The results of our NMA could help define a profile of patient responder or resistant to specific classes of immune drugs and can be used to guide/design future studies in the novel scenario of precision immune-oncology.
Botticelli A
，Cirillo A
，Strigari L
，Valentini F
，Cerbelli B
，Scagnoli S
，Cerbelli E
，Zizzari IG
，Rocca CD
，D'Amati G
，Polimeni A
，Nuti M
，Merlano MC
，Mezi S
，Marchetti P
... -
《Frontiers in Immunology》
Immune Checkpoint Inhibitors for Patients With Advanced Non-Small-Cell Lung Cancer: A Systematic Review.
Second-line treatment options are limited for patients with advanced non-small-cell lung cancer (NSCLC). Standard therapy includes the cytotoxic agents docetaxel and pemetrexed, and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors erlotinib and gefitinib. Immune checkpoint inhibitors are a new class of treatment that have shown durable overall radiologic response rates and have been well tolerated. The objective of this systematic review was to investigate the efficacy of immune checkpoint inhibitors compared with other chemotherapies in patients with advanced NSCLC. Medline, Embase, and PubMed were searched for randomized controlled trials comparing treatment with immune checkpoint inhibitors against treatment with chemotherapy in patients with stage IIIB or IV NSCLC. Nine randomized controlled trials with 15 publications were included. A significant overall survival benefit of second-line nivolumab (nonsquamous: hazard ratio [HR] = 0.72, 95% confidence interval [CI], 0.60-0.77; P < .001; squamous: HR = 0.59, 95% CI, 0.44-0.79; P < .001) or second-line atezolizumab (HR = 0.73, 95% CI, 0.62-0.87; P = .0003) or second-line pembrolizumab (in patients with programmed cell death ligand 1 [PD-L1]-positive tumors) (pembrolizumab 2 mg/kg HR = 0.71, 95% CI, 0.58-0.88; P = .0008; pembrolizumab 10 mg/kg HR = 0.61, 95% CI, 0.49-0.75; P < .0001) or first-line pembrolizumab (HR = 0.60, 95% CI, 0.41-0.89; P = .005) compared with chemotherapy was found. The adverse effects were mainly higher in the chemotherapy arms. For patients with advanced stage IIIB/IV NSCLC, the improvement in overall survival outweighed the harms and supported the use of first-line pembrolizumab (in patients with ≥ 50% PD-L1-positive tumors) or second-line nivolumab, atezolizumab, or pembrolizumab (in patients with PD-L1-positive tumors).
Ellis PM
，Vella ET
，Ung YC
《-》
ResearchGate
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钛学术
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