First-line or second-line PD-1 inhibition in advanced oesophageal squamous cell carcinoma: A prospective, multicentre, registry study.

WHAT IS KNOWN AND OBJECTIVE: First-line and second-line immunotherapy with programmed death-1 (PD-1) inhibitors both improve overall survival in patients with advanced oesophageal squamous cell cancer (ESCC). This study explored survival differences between first-line and second-line PD-1 inhibition in advanced ESCC. METHODS: This registry study included 167 patients with advanced ESCC who were exposed to PD-1 inhibitors in either a first-line or a second-line setting between 15 January 2019 and 31 October 2020. The primary endpoint was overall survival, and secondary endpoints included overall tumour response, progression-free survival (PFS) and PFS2. A propensity score-matching (PSM) analysis was performed using the nearest-neighbour method. RESULTS AND DISCUSSION: Sixty-one patients started first-line treatment with chemotherapy and a PD-1 inhibitor (Group 1), while 106 started chemotherapy as the first-line choice and received a PD-1 inhibitor as the second-line choice (Group 2). The median PFS was 7.1 months in Group 1 and 4.1 months in Group 2 (log-rank p = 0.001). The median PFS2 was 7.1 months in Group 1 and 7.4 months in Group 2 (log-rank p = 0.4). Before PSM, the median overall survival was 13.5 months in Group 1 and 14.1 months in Group 2 (log-rank p = 0.9), and the sensitivity analysis showed consistent results (14.0 vs. 14.1 months). After PSM, the median overall survival rates for Group 1 (n = 61) and Group 2 (n = 61) were 13.5 and 13.1 months (log-rank p = 0.7) respectively. WHAT IS NEW AND CONCLUSION: In this study, patients with advanced ESCC who received first-line or second-line PD-1 inhibitors seemed to have comparable overall survival.

Erlotinib-based targeted dual agent versus erlotinib alone in previously treated advanced non-small-cell lung cancer: a meta-analysis of 13 randomized controlled trials.

OBJECTIVES: To compare the effects of an erlotinib-based targeted dual agent with erlotinib alone in previously treated patients with advanced non-small lung cancer (NSCLC). PATIENTS AND METHODS: The PubMed and Embase databases and the Cochrane Central Register of Controlled Trials were searched for publications between January 2005 and March 2016. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CIs were derived. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were assessed. RESULTS: Thirteen trials with a total of 4509 patients were included in this meta-analysis. Compared with erlotinib alone, combination therapy showed no improvement in OS (HR = 0.95; 95% CI, 0.89-1.02; P = .132) though significantly prolonged PFS (HR = 0.82; 95% CI, 0.75-0.90; P < .001). Combination therapy significantly increased ORR (RR = 1.32; 95% CI, 1.09-1.60; P = .005) and DCR (RR = 1.26; 95% CI, 1.17-1.36, P < .001). Sub-analysis assessment failed to identify any sub-groups which could benefit from combination therapy in terms of OS. Combination therapy was associated with more grade 3 or higher toxic effects (RR = 1.54; 95% CI, 1.22-1.95; P < .001). Patients treated with combination therapy had more grade 3 or greater fatigue (RR = 1.49; 95% CI, 1.16-1.91; P = .002), but did not develop more diarrhea (RR = 2.02; 95% CI, 0.86-4.77; P = .107) or rash (RR = 1.29, 95% CI, 0.90-1.85; P = .172). This study had limitations about heterogeneities among the included trials, and the analysis was not based on individual patient data. CONCLUSIONS: Compared with erlotinib alone, the erlotinib-based targeted dual agent showed a minimal magnitude of improvement in PFS but did not improve OS. The role of erlotinib-based combinations in previously treated patients with NSCLC seemed insignificant.

Angiogenesis inhibitors for patients with ovarian cancer: a meta-analysis of 12 randomized controlled trials.

OBJECTIVES: To investigate the effects of angiogenesis inhibitors in the treatment of patients with advanced or recurrent ovarian cancer, a meta-analysis was performed and overall survival (OS), progression-free survival (PFS), and toxicity were assessed. PATIENTS AND METHODS: The PubMed and Embase databases, and the Cochrane Central Register of Controlled Trials were searched for publications between January 2000 and June 2015. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CIs were derived. RESULTS: The 12 trials in this meta-analysis were divided into three groups: four trials with a VEGF inhibitor (the bevacizumab group), six trials with VEGFR inhibitors (the VEGFRIs group), and two trials with an angiopoietin inhibitor (the trebananib group). PFS improvement was seen in all groups (HR = 0.61, 95% CI 0.48 to 0.79, P < 0.001 for bevacizumab; HR = 0.71, 95% CI 0.59 to 0.87, P = 0.001 for VEGFRIs; and HR = 0.67, 95% CI 0.62 to 0.72, P < 0.001 for trebananib). Regarding OS, bevacizumab showed a trend of improvement (HR = 0.90, 95% CI 0.80 to 1.01, P = 0.079), VEGFRIs showed no improvement (HR = 0.92, 95% CI 0.75 to 1.11, P = 0.368), and trebananib demonstrated a significant prolongation (HR = 0.81, 95% CI 0.67 to 0.99, P = 0.036). Bevacizumab was associated with more class-specific adverse events (RR = 4.05, 95% CI 1.99 to 8.27, P < 0.001). Although the toxicity profiles differed, VEGFRIs developed common higher incidences of hypertension, diarrhea, and fatigue. A higher incidence of edema was reported in the trebananib group (RR = 2.60, 95% CI 0.84 to 8.00, P = 0.097). CONCLUSIONS: Anti-angiogenic therapy showed clear PFS benefit with increased toxicity, but its role in OS was undefined for ovarian cancer which emphasized the need for patient selection.

Maintenance treatment with different strategies in advanced non-small-cell lung cancer: a systematic review and meta-analysis.

A meta-analysis of all relevant randomized controlled trials (RCTs) was performed to assess the role of maintenance therapy with either a continuation or a switch strategy in the treatment of non-small-cell lung cancer and to investigate improvement in overall survival (OS) and progression-free survival (PFS). Depending on the tumor histologic type (squamous or nonsquamous), OS and PFS were also investigated. We used electronic databases to search for publications reporting RCTs comparing maintenance therapy and placebo or observation from January 1990 to March 2012. The primary endpoint of OS and the secondary endpoint of PFS were analyzed. Hazard ratios (HRs) with their 95% confidence intervals (CIs) were derived. Eleven trials of 4790 patients were eligible for this analysis. A trend of improved OS was found in continuation maintenance therapy, despite a lack of statistical significance (HR 0.82; 95% CI, 0.66-1.01; P = .06). Improved OS with statistical significance was seen in switch maintenance therapy (HR, 0.80; 95% CI, 0.72-0.90; P = .0002). PFS benefit was found with both continuation (HR, 0.54; 95% CI, 0.46-0.63; P < .00001) and switch maintenance therapy (HR, 0.64; 95% CI, 0.59-0.70; P < .00001). The squamous subgroup analysis demonstrated no statistically significant differences in either OS (HR, 0.91; 95% CI, 0.63-1.30; P = .60) or PFS (HR, 0.80; 95% CI, 0.58-1.10; P = .17), whereas the nonsquamous subgroup analysis revealed an improvement in both OS (HR, 0.78; 95% CI, 0.64-0.94; P = .009) and PFS (HR, 0.56; 95% CI, 0.50-0.63; P < .00001). Maintenance therapy was associated with higher drug-related grade 3 or greater toxic effects but without harming the patients' quality of life. Maintenance therapy with either a continuation or a switch strategy significantly increased PFS but OS was significantly improved only with the switch strategy. Patients with a nonsquamous histologic subgroup seemed to be more suitable for maintenance therapy.