First-line immune-based combination therapies for advanced non-small cell lung cancer: A Bayesian network meta-analysis.
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ABSTRACT: Background
Immune-based combination therapies have revolutionized the first-line treatment for advanced non-small cell lung cancer (NSCLC). However, for the efficacy and safety, the best treatment option is still uncertain.Methods
We conducted a Bayesian network meta-analysis of randomized controlled trials (RCTs) to evaluate first-line immune-based combination therapies for advanced NSCLC.Results
Fourteen trials involving 8467 patients were included. For the programmed cell death-ligand 1 (PD-L1) expression non-selective patients, there were no significant differences among all the treatment modes for overall survival (OS), but the ranking profiles indicated that Immunotherapy + Immunotherapy + Chemotherapy (IO + IO + Chemo) was most likely to be the best mode (probability = 68%). Immunotherapy + Immunotherapy + Anti-angiogenic therapy + Chemotherapy (IO + Anti-angio + Chemo) was significantly better than most other treatment modes for progression-free survival (PFS) with better objective response rate (ORR) and more obvious grade ≥3 treatment-related adverse events (TRAEs). In PD-L1-high cohort, IO + Anti-angio + Chemo seemed to be the best mode for OS, PFS, and ORR according to the ranking profiles. In PD-L1-intermediate and PD-L1-negative cohort, IO + IO + Chemo was inclined to be ranked first for prolonging OS (probability = 78%; 37%) and IO + Anti-angio + Chemo was most likely to provide best PFS (probability = 96%; 100%).Conclusion
IO + IO + Chemo has great potential to improve the OS regardless of histology type, especially in PD-L1-intermediate and PD-L1-negative cohort. IO + Anti-angio + Chemo shows great superiority in improving the short-term survival accompanied by increasing grade ≥3 TRAEs.
SUBMITTER: Mao Z
PROVIDER: S-EPMC8683544 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:It remains unknown which is the optimal first-line treatment regimen for patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). We performed a network meta-analysis to address this important issue. METHODS:PubMed, Embase, Cochrane Library, Web of Science and major international scientific meetings were searched for relevant randomized controlled trials (RCTs). Progression-free survival (PFS) data was the primary outcome of interest, and overall survival (OS) and serious adverse events (SAEs) were the secondary outcomes of interests, reported as hazard ratio (HR) or odds ratio (OR) and 95% confidence intervals (CIs). RESULTS:25 RCTs with a total of 5005 patients randomized to receive seven treatments were included in the meta-analysis. Third-generation tyrosine kinase inhibitor (TKI) (osimertinib) and first-generation TKIs (F-TKIs) in combination with chemotherapy (F-TKIs+CT) were more effective than F-TKIs alone in terms of PFS (HR = 0.46, 95% CI: 0.22-0.93; P = 0.031 and HR = 0.62, 95% CI: 0.39-0.98; P = 0.041) and OS (HR = 0.63, 95% CI: 0.43-0.91; P = 0.014 and HR = 0.73, 95% CI: 0.57-0.92; P = 0.008). Second-generation TKIs (S-TKIs) showed significant OS advantage over F-TKIs (HR = 0.83, 95% CI: 0.70-0.99; P = 0.04). Based on treatment ranking in terms of PFS and OS, osimertinib had the highest probability of being the most effective treatment (89% and 86%) and with the best tolerability. F-TKIs+CT was ranked the second-most effective regimen, but with relatively high risk of SAEs. CONCLUSIONS:Osimertinib seemed to be the most preferable first-line treatment in advanced EGFR-mutated NSCLC. However, limitations of the study including a single RCT investigating osimertinib and immature OS data need to be considered.
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Project description:BackgroundSeveral novel immune checkpoint inhibitor (ICI)-based treatments exhibited promising survival benefits for metastatic renal cell carcinoma (mRCC), yet there is no current guidance regarding the optimum first-line regimen. We performed this network analysis to compare the efficacy and safety of all available treatments for mRCC.MethodsA systematic search of literature was conducted up to April 30, 2019, and the analysis was done on a Bayesian fixed-effect model.FindingsTwenty-five randomized clinical trials (RCTs) involving 13,010 patients were included in this study. The results showed that for overall survival, pembrolizumab plus axitinib (hazard ratio [HR]: 0.53; 95% credible interval [CrI]: 0.38-0.73) and nivolumab plus ipilimumab (HR: 0.63; 95% CrI: 0.50-0.79) were significantly more effective than sunitinib, and pembrolizumab plus axitinib was probably (68%) to be the best choice. For progression-free survival, cabozantinib (HR: 0.66; 95% CrI: 0.46-0.94), pembrolizumab plus axitinib (HR: 0.69; 95% CrI: 0.57-0.84), avelumab plus axitinib (HR: 0.69; 95% CrI: 0.56-0.85), nivolumab plus ipilimumab (HR: 0.82; 95% CrI: 0.68-0.99), and atezolizumab plus bevacizumab (HR: 0.86; 95% CrI: 0.74-0.99) were statistically superior to sunitinib, and cabozantinib was likely (43%) to be the preferred options. Nivolumab plus ipilimumab (OR: 0.50; 95% CrI: 0.28-0.84), and atezolizumab plus bevacizumab (OR: 0.56; 95% CrI: 0.36-0.83) were associated with significantly lower rate of high-grade adverse events than sunitinib.InterpretationOur findings demonstrate that pembrolizumab plus axitinib might be the best treatment for mRCC, while nivolumab plus ipilimumab has the most favorable balance between efficacy and acceptability, and may provide new guidance to make treatment decisions. FUND: This research was supported by the Henan Provincial Scientific and Technological Research Project (Grant No. 192102310036).
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Project description:PurposeNivolumab, a fully human immunoglobulin G4 programmed death-1 immune checkpoint inhibitor antibody, has demonstrated improved survival in previously treated patients with advanced non-small-cell lung cancer (NSCLC). CheckMate 012, a phase I, multicohort study, was conducted to explore the safety and efficacy of nivolumab as monotherapy or combined with current standard therapies in first-line advanced NSCLC. Here, we report results for nivolumab plus platinum-based doublet chemotherapy (PT-DC).Patients and methodsPatients (N = 56) received nivolumab (intravenously) plus PT-DC concurrently every 3 weeks for four cycles followed by nivolumab alone until progression or unacceptable toxicity. Regimens were nivolumab 10 mg/kg plus gemcitabine-cisplatin (squamous) or pemetrexed-cisplatin (nonsquamous) or nivolumab 5 or 10 mg/kg plus paclitaxel-carboplatin (all histologies). The primary objective was to assess safety and tolerability. Secondary objectives included objective response rate and 24-week progression-free survival rate (per Response Evaluation Criteria in Solid Tumors version 1.1); exploratory objectives included overall survival (OS) and response by tumor programmed death ligand-1 expression.ResultsNo dose-limiting toxicities occurred during the first 6 weeks of treatment. Forty-five percent of patients (25 of 56 patients) reported grade 3 or 4 treatment-related adverse events (AEs); 7% of patients (n = 4) had pneumonitis. Twenty-one percent of patients (n = 12) discontinued all study therapy as a result of treatment-related AEs. Objective response rates for nivolumab 10 mg/kg plus gemcitabine-cisplatin, nivolumab 10 mg/kg plus pemetrexed-cisplatin, nivolumab 10 mg/kg plus paclitaxel-carboplatin, and nivolumab 5 mg/kg plus paclitaxel-carboplatin were 33%, 47%, 47%, and 43%, respectively; 24-week progression-free survival rates were 51%, 71%, 38%, and 51%, respectively; 2-year OS rates were 25%, 33%, 27%, and 62%, respectively. Responses were achieved regardless of tumor programmed death ligand-1 expression.ConclusionThe safety profile of nivolumab plus PT-DC was consistent with that expected for individual agents; however, treatment discontinuation related to AEs was greater with the combination. Encouraging activity was observed, especially for the nivolumab 5 mg/kg plus paclitaxel-carboplatin group, with a 2-year OS rate of 62%.
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