Checkpoint inhibitors in combination with chemotherapy for first-line treatment of advanced non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials (RCTs).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20558-e20558
Author(s):  
Wai Lin Thein ◽  
Aung Tun ◽  
Kyaw Zin Thein ◽  
Elizabeth Guevara
Keyword(s):  
Advanced Nsclc ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Small Cell ◽  
High Grade ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
Standard Chemotherapy ◽  
First Line Treatment

e20558 Background: Non-small cell lung cancer (NSCLC) accounts for ~85% of lung cancers among which the metastatic disease represents ~ 57%, and long-term prognosis remains poor. Combined chemoimmunotherapy can have synergistic anticancer activities through the immunomodulatory impact of checkpoint inhibitors and the immunogenic effect of chemotherapy. Methods: We systematically conducted a comprehensive literature search using PUBMED, EMBASE and SCOPUS databases through January 31, 2019. RCTs of first-line chemotherapy +/- immunotherapy in patients with advanced NSCLC were incorporated in the analysis. A generic inverse variance method was used to calculate the estimated pooled Hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS). The mantel-haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI) for pooled overall response rate (ORR), all-grade adverse events (AEs), and high-grade AEs (grade 3). Heterogeneity was assessed with Cochrane Q -statistic. Random effects were used due to significant heterogeneity among studies. Results: Nine phase 2 & 3 RCTs (Keynote – 021,189, 407, IMpower – 130, 131, 132, 150, checkmate-227, and Govindan et al) including 5042 patients with advanced NSCLC patients were included in the meta-analysis. The study arm used standard chemotherapy regimens in combination with ipilimumab, pembrolizumab, atezolizumab, or nivolumab while control arm used only standard chemotherapy regimens. The pooled HR for PFS was 0.65 (95% CI: 0.57-0.73; P = 0.00001), the pooled HR for OS was 0.72 (95% CI: 0.61-0.86; P = 0.0003), and the pooled RR for ORR was 1.45 (95 CI: 1.23-1.72; P = 0.0001). The pooled RRs for all-grade AEs and high-grade AEs were 1.03 (95% CI: 0.99-1.07; P = 0.13) and 1.21 (95% CI: 1.1-1.34; P = 0.0001), respectively. Conclusions: The combined chemoimmunotherapy can significantly improve PFS, OS, and ORR compared to standard chemotherapy for the first-line treatment of advanced NSCLC. The combined regimen results in a slightly higher risk of high-grade AEs without a significant increase in the risk of all-grade AEs.

Checkpoint inhibitors in combination with chemotherapy for first-line treatment of advanced squamous non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials (RCTs).

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 121-121
Author(s):  
Aung Tun ◽  
Wai Lin Thein ◽  
James Gasperino ◽  
Aymen Elfiky ◽  
Elizabeth Guevara
Keyword(s):  
Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Small Cell ◽  
High Grade ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
Standard Chemotherapy ◽  
First Line Treatment

121 Background: Squamous Non-small cell lung cancer (NSCLC) accounts for ~30% of lung cancers, and long-term survival remains poor for advanced disease. Combined chemo-immunotherapy can have synergistic anticancer activities through the immunomodulatory impact of checkpoint inhibitors and the immunogenic effect of chemotherapy. Methods: We systematically conducted a comprehensive literature search using PUBMED, EMBASE and SCOPUS databases through October 1, 2018. RCTs of first-line chemotherapy +/- immunotherapy in patients with advanced squamous NSCLC were incorporated in the analysis. A generic inverse variance method was used to calculate the estimated pooled Hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS). The mantel-haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI) for pooled overall response rate (ORR), all-grade adverse events (AEs), and high-grade AEs (≥grade 3). Heterogeneity was assessed with Cochrane Q -statistic. Random effects were used due to significant heterogeneity among studies. Results: Three phase 3 RCTs (Keynote – 407, IMpower – 131, and Govindan et al) including 1991 patients with advanced squamous NSCLC patients were included in the meta-analysis. The study arm used standard chemotherapy regimens in combination with ipilimumab, pembrolizumab, or atezolizumab, while control arm used only standard chemotherapy regimens. The pooled HR for PFS was 0.71 (95% CI: 0.56-0.9; P = 0.005), the pooled HR for OS was 0.84 (95% CI: 0.68-1.04; P = 0.11), and the pooled RR for ORR was 1.19 (95 CI: 0.9-1.56; P = 0.22). The pooled RRs for all-grade AEs and high-grade AEs were 1.17 (95% CI: 0.99-1.39; P = 0.07) and 1.36 (95% CI: 1.19-1.56; P = 0.0001), respectively. Conclusions: The combined chemo-immunotherapy improves PFS without significant improvement in OS & ORR compared to standard chemotherapy for the first-line treatment of advanced squamous NSCLC. The combined regimen results in a slightly higher risk of high-grade AEs without a significant increase in the risk of all-grade AEs.

scholarly journals Checkpoint inhibitors plus chemotherapy for first-line treatment of advanced non-small cell lung cancer: a systematic review and meta-analysis of randomized controlled trials

2019 ◽  
Vol 5 (9) ◽  
pp. FSO421 ◽  
Author(s):  
Aung Myint Tun ◽  
Kyaw Zin Thein ◽  
Wai Lin Thein ◽  
Elizabeth Guevara
Keyword(s):  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Objective Response ◽  
Small Cell ◽  
High Grade ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
First Line Treatment

Background: We conducted a meta-analysis to evaluate the efficacy and safety of upfront add-on immunotherapy for advanced non-small cell lung cancers (NSCLC). Methods: We performed a literature search on first-line chemotherapy ± immunotherapy in NSCLC. We utilized Revman version 5.3 to calculate the estimated pooled hazard ratio for overall survival (OS) and progression-free survival (PFS) and pooled risk ratio for objective response rate (ORR), all-grade and high-grade adverse events with 95% CI. Results: We analyzed 4322 patients. The pooled hazard ratios for OS, PFS and ORR were 0.74 (95% CI: 0.62–0.88; p = 0.0007), 0.62 (95% CI: 0.57–0.68; p = 0.00001) and 1.51 (95% CI: 1.3–1.74; p = 0.00001), respectively. The pooled risk ratios for all-grade and high-grade adverse events were 1.01 (95% CI: 0.99–1.03; p = 0.27) and 1.17 (95% CI: 1.07–1.28; p = 0.0006), respectively. Conclusion: Add-on immunotherapy significantly improves PFS, OS and ORR for the first-line treatment of advanced NSCLC with a reasonable safety profile.

Checkpoint inhibitors in combination with chemotherapy for first-line treatment of advanced non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials (RCTs).

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 117-117
Author(s):  
Aung Tun ◽  
Wai Lin Thein ◽  
Aymen Elfiky ◽  
James Gasperino ◽  
Elizabeth Guevara
Keyword(s):  
Standard Treatment ◽  
Advanced Nsclc ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
High Grade ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
Treatment Regimens ◽  
First Line Treatment

117 Background: Non-small cell lung cancer (NSCLC) accounts for ~85% of lung cancers among which the metastatic disease represents ~ 57%, and long-term prognosis remains poor. Combined chemo-immunotherapy can have synergistic anticancer activities through the immunomodulatory impact of checkpoint inhibitors and the immunogenic effect of chemotherapy. Methods: We systematically conducted a comprehensive literature search using PUBMED, EMBASE and SCOPUS databases through October 1, 2018. RCTs of first-line chemotherapy +/- immunotherapy in patients with advanced NSCLC were incorporated in the analysis. A generic inverse variance method was used to calculate the estimated pooled Hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS). The mantel-haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI) for pooled overall response rate (ORR), all-grade adverse events (AEs), and high-grade AEs (≥ grade 3). Heterogeneity was assessed with Cochrane Q-statistic. Random effects were used due to significant heterogeneity among studies. Results: Seven phase 2 & 3 RCTs (Keynote-021,189, 407, IMpower-131, 150, checkmate-227, and Govindan et al) including 3785 patients with advanced NSCLC were included in the analysis. IMpower 150 trial allowed EGFR or ALK mutated patients. The study arm used standard treatment regimens in combination with ipilimumab, pembrolizumab, atezolizumab, or nivolumab, while control arm used only standard treatment regimens. The pooled HR for PFS was 0.65 (95% CI: 0.56-0.77; P=0.00001), the pooled HR for OS was 0.73 (95% CI: 0.59-0.90; P=0.003), and the pooled RR for ORR was 1.45 (95 CI: 1.17-1.8; P=0.0007). The pooled RRs for all-grade AEs and high-grade AEs were 1.1 (95% CI: 1-1.21; P=0.05) and 1.28 (95% CI: 1.13-1.46; P=0.0001), respectively. Conclusions: Adding immunotherapy to standard regimen significantly improves PFS, OS, and ORR for the first-line treatment of advanced NSCLC. The combined regimen results in a slightly higher risk of high-grade AEs without a significant increase in the risk of all-grade AEs.

scholarly journals Effectiveness and Safety of Adding Bevacizumab to Platinum-Based Chemotherapy as First-Line Treatment for Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Yi Liu ◽  
Hui-Min Li ◽  
Ran Wang
Keyword(s):  
Lung Cancer ◽  
Advanced Nsclc ◽  
Meta Analysis ◽  
Small Cell ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
Platinum Based Chemotherapy ◽  
Subgroup Analyses ◽  
First Line Treatment

Background and Objective: Previous studies have evaluated the efficacy (OS, overall survival; PFS, progression-free survival; ORR, objective response rate) and adverse events of bevacizumab combined with platinum-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer (NSCLC) compared with chemotherapy alone. However, the results were inconsistent.Methods: We conducted a comprehensive search of PubMed, EMBASE, and Cochrane Library for potentially eligible articles. The outcomes were evaluated in terms of risk ratio (RR) or hazard ratio (HR) and the associated 95% confidence intervals (CIs). Meta-analysis was performed using the Stata 12.0 software, and subgroup analyses were performed based on the treatment and bevacizumab dose.Results: Six randomized controlled trials with 2,465 patients were included in this meta-analysis. The results demonstrated that bevacizumab significantly increased OS (HR = 0.87, 95% CI 0.79–0.96), extended PFS (HR = 0.65, 95% CI 0.54–0.77), and increased ORR (ES = 0.40, 95% CI 0.31–0.48) when added to first-line platinum-based chemotherapy in patients with advanced NSCLC. Subgroup analyses showed that only the higher dose (15 mg/kg) of bevacizumab plus carboplatin–paclitaxel significantly extended the OS and PFS, but both 7.5 mg/kg and 15 mg/kg of bevacizumab improved ORR. However, both 7.5 mg/kg and 15 mg/kg of bevacizumab could only increase PFS and ORR, but not extend OS, when added to cisplatin–gemcitabine. Bevacizumab significantly increased the risk of grade ≥3 events of febrile neutropenia, haemorrhagic events, hypertension, leukopenia, neutropenia, and proteinuria.Conclusion: Bevacizumab significantly increases OS, PFS, and ORR when added to first-line platinum-based chemotherapy in patients with advanced NSCLC, with no new safety signals found. Moreover, bevacizumab (15 mg/kg) plus carboplatin–paclitaxel is a better alternative in increasing OS to carboplatin–paclitaxel and bevacizumab (7.5 mg/kg and 15 mg/kg) plus cisplatin–gemcitabine.

Comparative effectiveness of immune-checkpoint inhibitors as first-line treatment for advanced nonsquamous non-small cell lung cancer patients: A network meta-analysis and a systematic review.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21731-e21731
Author(s):  
Roberto Jorge Bitton ◽  
Natalia Jacob ◽  
Juan Manuel Carrera ◽  
Ezequiel Cayetano Perez
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Small Cell ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
Indirect Comparisons ◽  
First Line Treatment

e21731 Background: Over the last decade six different immune-checkpoint inhibitors (ICI) have obtained approval in 42 tumor types, several of them are indeed competing for the same indication and there is a lack of direct comparative data to guide the medical oncologist. Network meta-analysis (NMA) is a technique developed as an extension of pairwise meta-analysis to allow comparisons of multiple treatments, using both direct and indirect evidence. This NMA evaluates the effectiveness of several ICIs, either in combination or as single agents, as frontline therapy for patients with advanced non-squamous non-small cell lung cancer (NSCLC). Methods: We conducted a systematic review of randomized controlled trials (RCT) through Pubmed, Embase, Cochrane Central register of Controlled trial databases, Clinicaltrial.gov database and ASCO abstracts (up to June 2019), to identify phase III RCTs on advanced non-squamous NSCLC in the first-line setting. Both the search and study screening were performed for two independent reviewers. NMA of survival outcomes in different subsets of PD-L1 expression groups was performed and ICIs indirect comparisons were performed. Results: 6 RCTs with 5860 patients were included for the NMA. ICIs were evaluated in combination with several chemotherapy regimens and in the case of Nivolumab in combination with ipilimumab. Atezolizumab was evaluated in one of the RCTs in combination with chemotherapy and bevacizumab. Both Pembrolizumab and Nivolumab were evaluated as monotherapy, either in a separate treatment arms within a trial or in a separate trial. Overall ICI in combination improved survival across PD-L1 expression level subgroups compared with chemotherapy (platinum doublets +/- bevacizumab). Indirect comparisons of ICIs in combination therapy for first-line treatment in advanced non-squamous NSCLC showed little evidence of differences between pembrolizumab or atezolizumab in combination with chemotherapy and nivolumab/ipilimumab. Evaluated as monotherapy pembrolizumab seems to have more evidence of effectiveness than nivolumab. Conclusions: ICIs in combination therapy improve survival in previously untreated advanced NSCLC across PD-L1 expression levels compared with standard first line chemotherapy regimens. There is little evidence of survival difference between pembrolizumab and atezolizumab in combination, and nivolumab requires a combination with ipilimumab to reach similar levels of effectiveness.

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