Comparative Efficacy and Safety of Programmed Death-1 Pathway Inhibitors in Advanced Gastroesophageal Cancers: A Systematic Review and Network Meta-Analysis of Phase III Clinical Trials

Background: The use of checkpoint inhibitors has changed the treatment landscape for gastroesophageal cancer in the third-line setting. However, success rates in earlier treatment lines are highly variable across trials. Herein, we compare the efficacy and safety of the different anti-PD-1/PD-L1 reg...

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Bibliographic Details
Published in:Cancers 2021-05, Vol.13 (11), p.2614
Main Authors: da Silva, Laercio Lopes, Aguiar, Pedro Nazareth, Park, Robin, Edelman Saul, Eduardo, Haaland, Benjamin, de Lima Lopes, Gilberto
Format: Article
Language:English
Subjects:
Bias
Cancer therapies
Chemotherapy
Clinical trials
ErbB-2 protein
Esophagus
Immune checkpoint
Immunotherapy
Meta-analysis
PD-1 protein
PD-L1 protein
Pembrolizumab
Safety
Survival
Systematic Review
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Summary:Background: The use of checkpoint inhibitors has changed the treatment landscape for gastroesophageal cancer in the third-line setting. However, success rates in earlier treatment lines are highly variable across trials. Herein, we compare the efficacy and safety of the different anti-PD-1/PD-L1 regimens with or without chemotherapy; Methods: We performed a network meta-analysis (NMA) of anti-PD-1/PD-L1 monotherapy or combined with chemotherapy (chemoimmunotherapy) for gastroesophageal cancers without ERBB2 overexpression; Results: The first-line NMA included four trials (N = 3817), showing that chemoimmunotherapy improved OS and PFS without significant safety difference: Nivolumab-chemotherapy, OS (HR: 0.83 [95% CI, 0.75–0.92]), PFS (HR 0.68 [95% CI, 0.57–0.81]), Pembrolizumab-chemotherapy: OS (HR 0.77 [95% CI, 0.67–0.88]), PFS (HR: 0.72 [95% CI, 0.60–0.85]. Pembrolizumab monotherapy was the safest first-line treatment, SAE (OR 0.02 [95% CI, 0.00–0.2]) but showed no survival benefit. The second-line NMA encompassed four trials (N = 2087), showing that anti-PD-1 significantly improved safety but not survival: camrelizumab, SAE (OR 0.37; [95% CI, 0.24–0.56]); nivolumab, SAE (OR 0.13, [95% CI, 0.08–0.2]) pembrolizumab, SAE (OR 0.4; [95% CI, 0.30–0.53]); Conclusions: chemoimmunotherapy improves OS and PFS in previously untreated gastroesophageal cancers. Anti-PD-1 monotherapies improve safety in refractory disease, with no significant survival benefit.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13112614