Sorafenib-based therapy in HER2-negative advanced breast cancer: Results from a retrospective pooled analysis of randomized controlled trials

Introduction: Ribociclib, a cyclin-dependent kinase 4/6 inhibitor, has improved survival in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER 2)-negative advanced breast cancer. Despite remarkable efficacy, potential cardiac toxicities remain a concern. We undertook a combined analysis of randomized controlled trials (RCT) to estimate the incidence of prolongation of corrected QT interval (QTcF) associated with ribociclib. Methods: We performed systematic search of Embase, MEDLINE, and meeting abstracts till September 30, 2018, to find all phase 3 RCTs comparing ribociclib with other agents or placebo in patients with advanced breast cancer and reporting QTc prolongation as adverse event. Mantel-Haenszel method was used to calculate the pooled risk ratio (RR) and absolute risk difference (RD) with 95% CI. Fixed effects model was applied. Heterogeneity was assessed using I2 statistic. Results: Three phase III studies with 2,062 participants were included. Randomization ratio was 1 to 1 in MONALEESA-2 and 7 studies and 2 to 1 in MONALEESA-3 study. I2 statistic was 0, suggesting homogeneity across studies. Prolongation of QTcF >60 msec from baseline was observed in 72 patients (61 had post-baseline QTcF >480 msec) in ribociclib arm, compared to 7 in control arm. Pooled RR for prolongation of QTcF was 7.956 (95%CI: 3.683–17.187; P<.001) and RD was 0.055 (95%CI: 0.040–0.070; P<.001). The risk of having a post-baseline QTcF >480 msec was significantly higher with ribociclib vs control (pooled RR, 4.002; 95%CI: 2.161–7.412; P<.001; and RD, 0.039; 95%CI: 0.024–0.055; P<.001). A total of 16 (1.38%) patients in the ribociclib arm had dose reduction, interruption, or discontinuation due to QTcF prolongation, as opposed to 3 (0.33%) in control arm. Pooled RR and RD were statistically significant at 4.204 (95%CI: 1.333–3.260; P=.014) and 0.012 (95%CI: 0.004–0.021; P=.006), respectively. Conclusion: Advanced breast cancer patients may have cardiac dysfunction due to prior cardiotoxic chemotherapies. In our meta-analysis, ribociclib was associated with significantly higher risk of QTc prolongation and the resultant dosing inconsistencies and discontinuation. Early detection of this potential adverse event and timely intervention are critical.

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Poly(ADP-Ribose) Polymerase Inhibitors (PARPi) for Patients With Advanced Breast Cancer: a Meta-analysis of Randomized Controlled Trials

10.21203/rs.3.rs-48500/v2 ◽

2020 ◽

Author(s):

YongCheng Su ◽

XiaoGang Zheng

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Advanced Breast ◽

Controlled Trials ◽

Randomized Controlled ◽

Polymerase Inhibitors

Abstract The authors have withdrawn this preprint due to erroneous posting.

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Efficacy and Safety of Aidi Injection as an Adjuvant Therapy on Advanced Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/2871494 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Yihui Chai ◽

Yunzhi Chen ◽

Wen Li ◽

Zhong Qin ◽

Jie Gao ◽

...

Keyword(s):

Breast Cancer ◽

Systematic Review ◽

Advanced Breast Cancer ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Advanced Breast ◽

Controlled Trials ◽

Efficacy And Safety ◽

Randomized Controlled ◽

Aidi Injection

Background. Aidi injection (ADI) is being used widely for breast cancer in China. However, the efficacy and safety of it need to be summarized. We conducted a systematic review and meta-analysis to compare ADI and non-ADI treatment for advanced breast cancer. Methods. We searched PubMed, EMBASE, CNKI, SinoMed, and CENTRAL from inception to Jan 2020 for randomized controlled trials (RCTs) with diagnosis of advanced breast cancer that compared the efficacy of ADI with non-ADI treatment. Two researchers screened the literature, extracted data, and evaluated risk of bias separately. The primary outcomes were overall response rate (ORR) and disease control rate (DCR). The secondary outcomes included the QOL, immune cells, and adverse events. Review Manager software was used for estimating risks of bias of included studies, data analysis, and plotting. The sensitivity analysis and the publication bias test were performed using the R language. I2 and chi-square tests were used to estimate heterogeneity. If P>0.1 or I2 < 40%, the fixed-effect model meta-analysis was performed. A random or fixed-effect analysis was used depending on the heterogeneity testing. Weighted mean difference (WMD) or standard mean difference (SMD) was used for analysis of continuous data, and the rate ratio (RR) was calculated for the dichotomous variable, respectively. Results. We included 14 studies with 1006 patients diagnosed as advanced breast cancer in total. The pooled effect showed that ADI increased ORR in advanced BC patients as an add-on therapy with little heterogeneity (RR = 1.14, 95% CI 1.03–1.27). DCR in BC patients could not be improved by ADI. ADI improved the KPS score in BC patients compared with chemotherapy alone (MD = 3.26, 95% CI 1.74–4.78). There were no improvements on immune markers except CD4/CD8 and NK%. Serum tumor markers CEA and CA153 were decreased while treated with ADI, but only one trial was involved. ADI decreased the numbers of myelosuppression in advanced BC patients, and AST, ALT, γ-GT, and CK-MB were all decreased. The sensitivity evaluation indicated that the result of the pooled effect size had good stability. Conclusion. This meta-analysis suggested that based on the existing evidence, treatment with ADI significantly changed the ORR of patients with advanced BC and improved their quality of life with few side effects. However, more randomized trials involving larger samples should be considered, and detailed mechanisms are needed to be uncovered.

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