scholarly journals PD-1/PD-L1 Inhibitors versus Chemotherapy for Previously Treated Advanced Gastroesophageal Cancer: A Meta-Analysis of Randomized Controlled Trials

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Zhong Maoxi ◽  
Xue Jinmin ◽  
Zeng Xiaozhu ◽  
Yue Yubing ◽  
Zhu Yuxi
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Cancer ◽  
Cell Carcinoma ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Line Treatment ◽  
Second Line ◽  
Gastroesophageal Cancer ◽  
Randomized Controlled ◽  
Previously Treated

Patients with advanced gastroesophageal cancer refractory to the previous regimen of chemotherapy suffered from poor prognosis without many effective treatment options. Immune checkpoint inhibitors (ICIs) provide promising efficacy, but the relevant clinical trials have offered controversial data. We performed this meta-analysis to compare the efficacy and safety of inhibitors against programmed cell death receptor 1 (PD-1) and its ligand PD-L1 versus chemotherapy as second or third-line therapy in patients with advanced gastroesophageal cancer. Six randomized controlled trials (RCTs) including 2,648 patients were included. The meta-analysis results indicated that both ORR (RR = 1.39, 95% CI: 0.85∼2.25, P  = 0.188) and PFS (HR = 1.14, 95% CI: 0.88∼1.46, P  = 0.316) were not significantly improved by ICIs compared with chemotherapy. However, the OS was significantly prolonged (HR = 0.85, 95% CI: 0.75–0.97, P  = 0.018) in the ICIs group compared with chemotherapy. Subgroup analysis showed that ICIs provide statistically significant OS benefits over chemotherapy in PD-L1-positive, squamous cell carcinoma, Asia origin, esophageal cancer, second-line treatment, male, and aged 65 or older patients. Compared with chemotherapy, the TRAEs risk of ICIs was reduced by 33% (RR = 0.67, 95% CI: 0.62–0.73, P  ≤ 0.001). And the risk of grades 3–5 of TRAEs was reduced by 60% (RR = 0.40, 95% CI: 0.33–0.49, P  ≤ 0.001). Compared to chemotherapy, ICIs appeared to improve OS and were better tolerated in previously treated patients with advanced esophageal cancer. We recommend PD-1/PD-L1 inhibitors as an optimal treatment option for positive PD-L1 expression, squamous cell carcinoma, Asia origin, esophageal cancer, second-line treatment, male, and ≥65 years of age patients.

scholarly journals PD-1/PD-L1 Inhibitors vs. Chemotherapy For Previously Treated Advanced Gastroesophageal Cancer: A Meta-Analysis of Randomized Controlled Trials

2021 ◽  
Author(s):  
Maoxi Zhong ◽  
Xiaozhu Zeng ◽  
Jinmin Xue ◽  
Yubing Yue ◽  
Yuxi Zhu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Cancer ◽  
Cell Carcinoma ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Line Treatment ◽  
Second Line ◽  
Gastroesophageal Cancer ◽  
Randomized Controlled ◽  
Previously Treated

Abstract Background: Patients with advanced gastroesophageal cancer refractory to previous regimen of chemotherapy suffered from poor prognosis without many effective treatment options. Immune checkpoint inhibitors (ICIs) provide promising efficacy, but the relevant clinical trials have offered controversial data. Therefore, we performed this meta-analysis to compare the efficacy and safety of inhibitors against programmed cell death receptor 1 (PD-1) and its ligand PD-L1 versus chemotherapy as second or third-line therapy in patients with advanced gastroesophageal cancer.Materials and methods: We systematically searched PubMed, Cochrane Library, Web of Science, Embase, and China National Knowledge Web. All studies regarding ICIs compared chemotherapy for advanced gastroesophageal cancer were included. Outcomes included the overall survival (OS)，progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse events (TRAEs). The hazard ratio (HR) and odds ratio (OR) were the principal measure of effect.Results: Finally we selected 7 randomized controlled trials (RCTs) including 3,141 patients. One study compared ICIs with placebo therapy only as reference. The meta-analysis was performed by combining 6 RCTs about the comparing ICIs with chemotherapy. Results indicated that both ORR (RR = 1.39, 95%CI 0.85-2.25, P = 0.188) and PFS (HR = 1.14, 95%CI 0.88-1.46, P = 0.316) were not significantly improved by ICIs compared with chemotherapy. However, the OS was significantly prolonged (HR = 0.85, 95%CI 0.75-0.97, P = 0.018) in ICIs group compared with chemotherapy. Subgroup analysis showed that ICIs provide statistically significant OS benefits over chemotherapy in patients of PD-L1 positive, squamous cell carcinoma, Asia origin, esophageal cancer, second-line treatment, male and patients aged 65 or older. Compared with chemotherapy, the TRAEs risk of ICIs was reduced by 33% (RR = 0.67, 95%CI 0.62-0.73, P = 0.000). And the risk of grade 3-5 TRAEs was reduced by 60% (RR = 0.40, 95%CI 0.33-0.49, P = 0.000). Conclusions: Compared to chemotherapy, ICIs appears to improve OS and are better tolerated in previously treated patients with advanced esophageal cancer. We recommend PD-1/PD-L1 inhibitors as an optimal treatment option for patients with positive PD-L1 expression, squamous cell carcinoma, Asia origin, esophageal cancer, second-line treatment, male and ≥65 years of age.

scholarly journals Meta-analysis examining overall survival in patients with pancreatic cancer treated with second-line 5-fluorouracil and oxaliplatin-based therapy after failing first-line gemcitabine-containing therapy: effect of performance status and comparison with other regimens

2020 ◽  
Author(s):  
Zev Aryeh Wainberg ◽  
Kynan Feeney ◽  
Myung Ah Lee ◽  
Andrés Muñoz ◽  
Antonio Cubillo Gracián ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Meta Analysis ◽  
Performance Status ◽  
Controlled Trials ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Similar Treatment ◽  
Randomized Controlled ◽  
Nanoliposomal Irinotecan

Abstract Background: Pancreatic cancer has a poor prognosis and few choices of therapy. For patients with adequate performance status, FOLFIRINOX or gemcitabine plus nab-paclitaxel are preferred first-line treatment. 5-Fluorouracil (5-FU)–based therapy (e.g. FOLFIRI, OFF, or FOLFOX) are often used in patients who previously received gemcitabine-based regimens. A systematic review was conducted of the safety and efficacy of FOLFOX for metastatic pancreatic cancer following prior gemcitabine-based therapy. A Bayesian fixed-effect meta-analysis with adjustment of patient performance status (PS) was conducted to evaluate overall survival (OS) and compare outcomes with nanoliposomal irinotecan combination therapy. Methods: PubMed.gov, FDA.gov, ClinicalTrials.gov, congress abstracts, Cochrane.org library, and EMBASE database searches were conducted to identify randomized controlled trials of advanced/metastatic disease, prior gemcitabine-based therapy, and second-line treatment with 5-FU and oxaliplatin. The database search dates were January 1, 1990–June 30, 2019. Endpoints were OS and severe treatment-related adverse events (TRAEs). Trial-level PS scores were standardized by converting Karnofsky grade scores to Eastern Cooperative Oncology Group (ECOG) Grade, and overall study-weighted PS was calculated based on weighted average of all patients. Results: Of 282 studies identified, 11 randomized controlled trials ( N = 454) were included in the meta-analysis. Baseline weighted PS scores predicted OS in 10 of the 11 studies, and calculated PS scores of 1.0 were associated with a median OS of 6.3 months (95% posterior interval, 5.4–7.4). After adjusting for baseline PS, FOLFOX had a similar treatment effect profile (median OS, range 2.6–6.7 months) as 5-FU/leucovorin plus nanoliposomal irinotecan therapy (median OS, 6.1 months; 95% confidence interval 4.8–8.9). Neutropenia and fatigue were the most commonly reported Grade 3–4 TRAEs associated with FOLFOX. Conclusions: Baseline PS is a strong prognostic factor when interpreting the efficacy of 5-FU and oxaliplatin-based therapy of pancreatic cancer after progression on first-line gemcitabine-based regimens. When baseline PS is considered, FOLFOX has a similar treatment effect as 5-FU and nanoliposomal irinotecan therapy and a comparable safety profile. These findings suggest that 5-FU and oxaliplatin-based therapies remain an acceptable and alternative second-line treatment option for patients with pancreatic cancer and adequate PS (e.g. ECOG 0–1) following gemcitabine treatment.

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