Monoclonal antibody(Normunity)

Rationale: Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality worldwide. Acute exacerbations are associated with progressive decline in lung function and quality of life. After recognition of the role of type 2 inflammation in the pathogenesis of eosinophilic COPD, there was increased interest in studying monoclonal antibodies as a therapeutic agent. Multiple randomized controlled trials showed promising results, yet no consensus exists. Objectives: Our study aims to summarize the current evidence regarding the role of monoclonal antibodies in the management of patients with eosinophilic COPD. Methods: We systematically searched multiple databases using prespecified search terms. We included only randomized controlled trials that compared monoclonal antibodies versus placebo in patients with objective evidence of eosinophilic COPD receiving standard-of-care therapy. The primary outcome of interest was the annualized rate of COPD exacerbation. Absolute changes in forced expiratory volume in 1 second and St. George's Respiratory Questionnaire scores were secondary outcomes. We also reported serious adverse effects and all-cause mortality. Statistical analysis was conducted via random effects model using RevMan software. Results: We identified and included eight double blinded, placebo-controlled trials with a total of 4,512 patients and a median follow up of 52 weeks. The patients' mean age was 65 ± 8 years, with 85% male. Seventy percent of patients were former smokers, with a mean of 43 ± 25 pack-years of smoking history. The majority of patients were receiving triple inhaled therapy. The mean serum eosinophil count at enrollment was 398 ± 297 cells/μl. The monoclonal antibodies studied were dupilumab, mepolizumab, benralizumab, astegolimab, and itepekimab. Compared with placebo, patients who received monoclonal antibodies had a significantly decreased annualized COPD exacerbation rate (rate ratio, 0.79; 95% confidence interval [CI], 0.73-0.86; P < 0.001). The serious adverse effect rate was significantly lower in the monoclonal antibody arm compared with placebo (odds ratio, 0.80; 95% CI, 0.69-0.93; P = 0.004). The all-cause mortality rates were not statistically different between the groups (odds ratio, 0.91; 95% CI, 0.63-1.3; P = 0.6). Dupilumab showed a trend of improved efficacy over mepolizumab and benralizumab. Conclusions: In patients with eosinophilic COPD receiving standard-of-care therapy, the use of monoclonal antibodies led to a significant reduction in annualized COPD exacerbation rate compared with placebo. Monoclonal antibodies have an acceptable tolerability and safety profile.

Immune checkpoint inhibitors (ICIs) + chemotherapy became standard her2-GC first line treatment.

The aim of this study is to investigate whether ICIs + chemo provides benefit for patients with low programmed death-ligand 1 (PD-L1) expression.

This study is a systematic review and meta-analysis.

We searched PubMed, Embase, Web of Science, and Cochrane Library as well as the 2019 to 2024 Annual Meetings of the European Society for Medical Oncology, the American Association for Cancer Research, the American Society of Clinical Oncology (ASCO), and the ASCO Symposium on Gastrointestinal Oncology (ASCO-GI) and the ClinicalTrials.gov database.

This systematic review included phase III randomized controlled trials comparing first-line immunotherapy combined with chemotherapy versus chemotherapy alone in advanced gastric cancer. KMSubtraction was used to estimate survival data for those trials that did not report data for the PD-L1 low-expression population.

We included a total of nine randomized clinical trials. In patients with combined positive score (CPS) < 1 and CPS < 5, monoclonal antibody + chemotherapy did not show an improvement in overall survival (OS) or progression-free survival (PFS) (CPS < 1 OS: hazard ratio (HR) = 0.91, 95% CI: 0.77–1.08; PFS: HR = 0.88, 95% CI: 0.73–1.07. CPS < 5 OS: HR = 0.92, 95% CI: 0.79–1.08; PFS: HR = 0.78, 95% CI: 0.53–1.14). However, in trials using dual antibodies, patients with PD-L1 CPS < 5 achieved improvements in PFS (HR = 0.64, 95% CI: 0.52–0.80). In trials using tumor area positivity (TAP) scoring, the subgroup with TAP < 5% did not achieve benefits in OS or PFS from immunotherapy plus chemotherapy (OS: HR = 0.92, 95% CI: 0.75–1.13; PFS: HR = 0.91, 95% CI: 0.74–1.13).

Our study results indicate that in the first-line treatment of advanced gastric cancer, monoclonal antibody combined with chemotherapy does not provide a survival benefit compared to chemotherapy alone for patients with low PD-L1 expression. However, it is noteworthy that in the COMPASSION-15 trial, patients with CPS < 5 achieve significant improvements in OS and PFS, which may be related to the bispecific antibodies and needs to be validated by further studies.

This study was registered in PROSPERO (CRD42024568972).