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BACKGROUND: Cyclin-dependent kinases (CDK) 4/6 inhibitors have significantly improved outcomes for patients with ER+/HER2- breast cancer. Nevertheless, they differ from each other in terms of chemical, biological, and pharmacological features, as well as toxicity profiles. We aim to determine whether QTc prolongation is caused by CDK4/6i in general or if it is associated with ribociclib only. METHODS: We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing the prevalence of QTc prolongation as an adverse event in HR+ breast cancer patients treated with CDK4/6i vs those without CDK4/6i. We pooled risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI) for the binary endpoint of QT prolongation. RESULTS: We included 14 RCTs comprising 16,196 patients, of whom 8,576 underwent therapy with CDK4/6i. An increased risk of QTc prolongation was associated with the use of CDK4/6i (RR 2.35; 95% CI 1.67-3.29; p < .001; I2=44%). Subgroup analyses revealed a significant increase in the QTc interval for the ribociclib and palbociclib cohorts. The ribociclib subgroup showed a risk ratio of 3.12 (RR 3.12; 95% CI 2.09-4.65; p < .001; I2 = 12%) while the palbociclib subgroup had a risk ratio of 1.51 (RR 1.51; 95% CI 1.05-2.15; p = .025, I2=0%). CONCLUSION: Palbociclib was associated with QTc prolongation, however, the RR for any grade QTc was quantitively twice with ribociclib. Furthermore, grade 3 QTc prolongations were observed exclusively with ribociclib. These results are important for guiding clinical decision-making and provide reassurance regarding the overall safety profile of this drug class.
RESUMEN
PURPOSE: Laparoscopic pancreatoduodenectomy (LPD) has emerged as an alternative to open technique in treating periampullary tumors. However, the safety and efficacy of LPD compared to open pancreatoduodenectomy (OPD) remain unclear. Thus, we conducted an updated meta-analysis to evaluate the efficacy and safety of LPD versus OPD in patients with periampullary tumors, with a particular focus on the pancreatic ductal adenocarcinoma patient subgroup. METHODS: According to PRISMA guidelines, we searched PubMed, Embase, and Cochrane Library in December 2023 for randomized controlled trials (RCTs) that directly compare LPD versus OPD in patients with periampullary tumors. Endpoints and sensitive analysis were conducted for short-term endpoints. All statistical analysis was performed using R software version 4.3.1 with a random-effects model. RESULTS: Five RCTs yielding 1018 patients with periampullary tumors were included, of whom 511 (50.2%) were randomized to the LPD group. Total follow-up time was 90 days. LPD was associated with a longer operation time (MD 66.75; 95% CI 26.59 to 106.92; p = 0.001; I2 = 87%; Fig. 1A), lower intraoperative blood loss (MD - 124.05; 95% CI - 178.56 to - 69.53; p < 0.001; I2 = 86%; Fig. 1B), and shorter length of stay (MD - 1.37; 95% IC - 2.31 to - 0.43; p = 0.004; I2 = 14%; Fig. 1C) as compared with OPD. In terms of 90-day mortality rates and number of lymph nodes yield, no significant differences were found between both groups. CONCLUSION: Our meta-analysis of RCTs suggests that LPD is an effective and safe alternative for patients with periampullary tumors, with lower intraoperative blood loss and shorter length of stay.