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).

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.

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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).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e20558 ◽

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.

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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

Future Science OA ◽

10.2144/fsoa-2019-0081 ◽

2019 ◽

Vol 5 (9) ◽

pp. FSO421 ◽

Cited By ~ 9

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.

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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).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.8_suppl.121 ◽

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.

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Immune checkpoint inhibitors, alone or in combination with chemotherapy, as first-line treatment for advanced non-small cell lung cancer. A systematic review and network meta-analysis

Lung Cancer ◽

10.1016/j.lungcan.2019.05.029 ◽

2019 ◽

Vol 134 ◽

pp. 127-140 ◽

Cited By ~ 22

Author(s):

Urania Dafni ◽

Zoi Tsourti ◽

Katerina Vervita ◽

Solange Peters

Keyword(s):

Lung Cancer ◽

Systematic Review ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Small Cell ◽

Line Treatment ◽

Small Cell Lung ◽

First Line ◽

First Line Treatment

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Gefitinib in Non Small Cell Lung Cancer

Journal of Biomedicine and Biotechnology ◽

10.1155/2011/815269 ◽

2011 ◽

Vol 2011 ◽

pp. 1-14 ◽

Cited By ~ 13

Author(s):

Raffaele Costanzo ◽

Maria Carmela Piccirillo ◽

Claudia Sandomenico ◽

Guido Carillio ◽

Agnese Montanino ◽

...

Keyword(s):

Lung Cancer ◽

Tyrosine Kinase ◽

Small Cell Lung Cancer ◽

Advanced Nsclc ◽

Small Cell ◽

Line Treatment ◽

Phase 2 ◽

Small Cell Lung ◽

First Line ◽

First Line Treatment

Gefitinib is an oral, reversible, tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) that plays a key role in the biology of non small cell lung cancer (NSCLC). Phase I studies indicated that the recommended dose of gefitinib was 250 mg/day. Rash, diarrhea, and nausea were the most common adverse events. The positive results obtained in early phase 2 clinical trials with gefitinib were not confirmed in large phase 3 trials in unselected patients with advanced NSCLC. The subsequent discovery that the presence of somatic mutations in the kinase domain of EGFR strongly correlates with increased responsiveness to EGFR tyrosine kinase inhibitors prompted phase 2 and 3 trials with gefitinib in the first line-treatment of EGFR-mutated NSCLC. The results of these trials have demonstrated the efficacy of gefitinib that can be now considered as the standard first-line treatment of patients with advanced NSCLC harbouring activating EGFR mutations.

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Angiogenesis inhibitor plus erlotinib versus erlotinib alone as first-line for advanced non-small cell lung-cancer harboring EGFR mutation.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.9569 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 9569-9569 ◽

Cited By ~ 1

Author(s):

Thierry Landre ◽

Gaetan Des Guetz ◽

Kader Chouahnia ◽

Boris Duchemann ◽

Jean F. Morere ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Egfr Mutation ◽

Advanced Nsclc ◽

Small Cell ◽

Line Treatment ◽

Small Cell Lung ◽

First Line ◽

Anti Vegf ◽

First Line Treatment

9569 Background: Erlotinib is indicated in first line treatment for patients with Non-Small-Cell-Lung cancer (NSCLC) harbouring EGFR mutation. Addition of anti-VEGF in combination with erlotinib in this setting is controversial. Methods: We performed a meta-analysis of randomized trials comparing VEGF inhibitor plus erlotinib with erlotinib alone in first line treatment for advanced NSCLC harbouring EGFR mutation. The outcomes included overall survival (OS), progression-free survival (PFS) objective response rate (ORR), and median duration of response (DOR). A fixed-effect model was used. Results: Four studies evaluated bevacizumab + erlotinib (ARTEMIS, NEJ026, J025667, Stinchcombe et al), and one study evaluated ramucirumab + erlotinib (RELAY). These five eligible studies included 1230 non-squamous NSCLC patients (654 with Ex19del and 568 with Leu858Arg);. Most of the patients were women (63%), Asian (85%) and non-smokers (60%), with a median age of 64 years. The combination (anti-VEGF + erlotinib) was significantly associated with improvement of PFS (hazards ratio [HR]: 0.59, 95%CI: 0.51-0.69, p < 0.00001). Improvement in PFS was seen across all subgroups analyzed. Interim analysis of OS (HR: 0.90, 95%CI; 0.68-1.19, p = 0.45) and ORR (odds ratio [OR], 1.19, 0.91-1.55, p = 0.21) were not statistically significant. DOR was statistically longer with combination (p < 0.005). Conclusions: For patients with untreated advanced NSCLC with EGFR mutation, the anti-VEGF combination with erlotinib, compared with erlotinib alone, is associated with significantly improved PFS and DOR, but mature data for OS are needed to confirm the benefit of this strategy.

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