Clinical benefit analysis of PD-1 inhibitors in patients with advanced, recurrent or metastatic cervical cancer: a meta-analysis and systematic review.

Purpose: This study aims to comprehensively evaluate the efficacy and safety of programmed cell death protein-1 (PD-1) in patients with advanced, recurrent, or metastatic cervical cancer (ARMCC) and identify the population that may benefit the most. Methods: We conducted a search of PubMed, EMBASE, and the Cochrane Collaboration Library from their inception to September 2023. We extracted and analyzed the results related to the efficacy and safety of PD-1 in patients with ARMCC. The primary endpoints included the overall objective response rate (ORR) and adverse events (AEs), while the secondary endpoints encompassed the 1-year overall survival (OS) rate, 1-year progression-free survival (PFS) rate, as well as OS and PFS. We used a random effects model to conduct a meta-analysis on single-group rates, and the Mantel-Haenszel method was utilized to compare the ORR and the incidence of AEs. Results: Our study included a total of 21 trials involving 2,097 patients. The ORR of the combination of PD-1 inhibitors with chemotherapy was 56.36%, the combination of PD-1 inhibitors with anti-angiogenic agents was 38.72%, the combination of PD-1 inhibitors with Cytotoxic T-lymphocyte antigen 4 inhibitors was 25.60%, and PD-1 inhibitor monotherapy was 15.99%. The subgroup analysis showed that the group of patients with squamous cell carcinoma (SCC) exhibited a significantly higher ORR compared to the non-SCC group in patients who received PD-1 inhibitors combined with other anti-tumor drugs (Odds Ratio =2.43, P=0.002). Additionally, the group of patients with a programmed death-ligand 1 combined positive score (PD-L1 CPS) ≥1 exhibited a significantly higher ORR compared to the PD-L1 CPS <1 group in patients who received PD-1 inhibitor monotherapy (OR=4.14, P=0.02). PD-1 inhibitor monotherapy or PD-1 inhibitors combined with chemotherapy did not significantly increase the incidence of all grades of adverse events (Relative Risk=0.99, p=0.788) or the incidence of serious adverse events (RR=0.99, p=0.788) compared to chemotherapy alone. Conclusion: PD-1 inhibitors demonstrate outstanding efficacy in the treatment of patients with ARMCC. Patients with SCC may benefit more from treatments including PD-1 inhibitors in combination with other anti-tumor drugs, and PD-L1 CPS ≥1 can be considered a favorable indicator of immune therapy response. Importantly, the use of PD-1 inhibitor monotherapy or PD-1 inhibitors in combination with chemotherapy did not lead to an increased incidence of AEs compared with chemotherapy alone, indicting safety during treatment. Systematic Review Registration: PROSPERO (CRD42023457945).

Microsatellite instability as a marker of prognosis: a systematic review and meta-analysis of endometrioid endometrial cancer survival data.

INTRODUCTION: To investigate whether microsatellite instability (MSI) is an important prognostic biomarker for endometrioid endometrial cancer (EEC). METHODS: The PubMed, EMBASE, and the Cochrane Cooperative Library databases were searched from inception to July 2021. Overall survival, disease-free survival, progression-free survival, EEC-specific survival, recurrence-free survival, and the recurrence rate were pooled to analyze the correlation between MSI and EEC. In addition, Egger's regression analysis and Begg's test were used to detect publication bias. RESULTS: 17 studies met the inclusion criteria and were included in our meta-analysis with a sample size of 4723, and the included patients with endometrioid cancer (EC) all were EEC. The pooled hazard ratios (HR) in patients with EEC showed that MSI was significantly associated with shorter overall survival [HR = 1.37, 95% confidence interval (CI) (1.00-1.86), p = 0.048, I2 = 60.6%], shorter disease-free survival [HR = 1.99, 95% CI (1.31-3.01), p = 0.000, I2 = 67.2%], shorter EEC-specific survival [HR = 2.07, 95% CI (1.35-3.18), p = 0.001, I2 = 31.6%] and a higher recurrence rate [Odds ratios (OR) = 2.72, 95% CI (1.56-4.76), p = 0.000, I2 = 0.0%]. In the early-stage EEC subgroup, MSI was significantly associated with shorter overall survival [HR = 1.47, 95% CI (1.11-1.95), p = 0.07], shorter disease-free survival [HR = 4.17, 95% CI (2.37-7.41), p = 0.000], and shorter progression-free survival [HR = 2.41, 95% CI (1.05-5.54), p = 0.039]. No significant heterogeneity was observed in overall survival (I2 = 20.9%), disease-free survival (I2 = 0.0%), or progression-free survival (I2 = 0.0%) in patients with early-stage EEC. Meanwhile, publication bias was not observed, and the p-value for Egger's test of overall survival, disease-free survival, and EEC-specific survival were p = 0.131, p = 0.068, and p = 0.987, respectively. CONCLUSION: MSI is likely an important biomarker for poor prognosis in patients with EEC, and this correlation is even more certain in patients with early-stage EEC.

Efficacy and Safety of Tapentadol Immediate Release Assessment in Treatment of Moderate to Severe Pain: A Systematic Review and Meta-Analysis.

Objective: To assess the efficacy and safety of tapentadol IR for moderate to severe pain compared to oxycodone IR. Methods: A search was carried out up to July 2015 for randomized controlled trials (RCTs) of tapentadol IR compared to placebo or oxycodone HCL IR 10 mg for moderate to severe pain. Studies were pooled by risk ratio (RR) and weighted mean differences (WMD) with 95% confidence interval (CI). Results: Nine RCTs (n = 3,961) were analyzed. In this meta-analysis, tapentadol IR (50-, 75-, and 100-mg doses) showed significant improvements in moderate to severe pain relief on the sum of pain intensity difference over 48 hours (SPID 48 ) scores ( P < 0.00001 or P = 0.01). No statistically significant difference among all three doses of tapentadol IR and oxycodone HCL IR 10 mg on both SPID 48 and total pain relief over 48 hours (TOTPAR 48 ) scores (all P > 0.05) was found. Compared with tapentadol IR 50 mg, tapentadol IR 75 mg demonstrated significant improvement in moderate to severe pain relief based on both SPID 48 and TOTPAR 48 scores (all P < 0.05). For total adverse events (AEs) incidence, tapentadol IR 50 and 75 mg were significantly lower than oxycodone HCL IR 10 mg. Incidence of nausea and constipation were significantly lower with either tapentadol IR 50 or 75 mg compared with oxycodone HCL IR 10 mg (all P < 0.05). Conclusions: Tapentadol IR 75 mg might be an optimal dose for moderate to severe pain control with fewer side effects. All three doses of tapentadol IR could provide comparable efficacy to oxycodone HCL IR 10 mg.