Laercio Lopes da Silva1, Pedro Nazareth Aguiar2, Robin Park1, Eduardo Edelman Saul3, Benjamin Haaland4, Gilberto de Lima Lopes5. 1. Metrowest Medical Center, Department of Medicine, Tufts University School of Medicine, Framingham, MA 02111, USA. 2. Faculdade de Medicina do ABC, Instituto Oncoclinicas, Av. Juscelino Kubitschek, 510, São Paulo 04543-906, SP, Brazil. 3. Department of Medicine, Jackson Memorial Hospital, University of Miami, Miami, FL 33136, USA. 4. Population Health Sciences and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA. 5. Division of Hematology-Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33146, USA.
Abstract
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.
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.
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