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1.
Medicine (Baltimore) ; 98(1): e13909, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30608416

ABSTRACT

BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (palbociclib and abemaciclib) and mammalian target of rapamycin (mTOR) inhibitors (everolimus) are effective agents for restoring endocrine sensitivity in patients with advanced breast cancer progression on prior aromatase inhibitors. We conducted a network meta-analysis to compare these treatments in terms of progression-free survival (PFS), objective response rate (ORR), and clinical benefit rate (CBR). METHODS: The PubMed and Embase databases were searched for relevant publications between January 2000 and June 2018. Treatments were ranked based on a network meta-analysis. Ranking was determined by P-score. A random-effect model was used when heterogeneity was detected; otherwise, a fixed-effect model was used. RESULTS: Six trials comprising 4063 patients formed the comparison network. Compared with everolimus plus exemestane, the combinations of palbociclib or abemaciclib with fulvestrant showed similar efficacies in PFS and no differences in ORR. For the CBR, palbociclib demonstrated improvement, while abemaciclib did not. Incidences of severe adverse events did not significantly differ. A total of 29%, 15.9%, and 4% of patients discontinued everolimus, abemaciclib, and palbociclib, respectively, due to toxicity. CONCLUSION: These results suggest similar efficacies between CDK4/6 inhibition and mTOR blockade; however, CDK4/6 inhibitors were associated with favorable toxicity profiles.


Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Postmenopause , Protein Kinase Inhibitors/therapeutic use , TOR Serine-Threonine Kinases/antagonists & inhibitors , Aminopyridines/therapeutic use , Androstadienes/therapeutic use , Benzimidazoles/therapeutic use , Breast Neoplasms/pathology , ErbB Receptors/metabolism , Everolimus/therapeutic use , Female , Fulvestrant/therapeutic use , Humans , Network Meta-Analysis , Piperazines/therapeutic use , Progression-Free Survival , Pyridines/therapeutic use
2.
Sci Rep ; 7(1): 16870, 2017 12 04.
Article in English | MEDLINE | ID: mdl-29203855

ABSTRACT

Definitive chemoradiotherapy (dCRT) is a treatment option for patients with localized esophageal squamous cell carcinoma (ESCC). We investigated consolidation chemotherapy (CCT) in patients with ESCC who attained clinical complete response after dCRT. Between January 2009 and December 2012, medical records of ESCC patients treated with dCRT were retrospectively reviewed, and those who attained CCR were identified. Progression-free survival and overall survival rates were estimated by the Kaplan-Meier method. The Cox regression model was used to determine prognostic factors. Of the 522 patients treated with dCRT, 209 patients achieved CCR, with 67 receiving consolidation chemotherapy (the CCT group) and 142 receiving dCRT alone (the control group). CCT did not prolong progression-free survival (33.0 vs 18.0 months, P = 0.07, HR = 0.70, 95% CI, 0.48-1.04); however, CCT improved the median overall survival (53.4 vs 27.0 months, P = 0.04, HR = 0.67, 95% CI, 0.44-0.99) compared with dCRT alone. CCT remained a favorable prognostic factor for overall survival in a multivariate analysis (HR = 0.59, P = 0.02); however, a propensity score analysis failed to show an additional overall survival benefit with CCT. In the present analysis, CCT did not improve progression-free survival but may have extended overall survival in ESCC patients who achieved complete clinical response after dCRT.


Subject(s)
Chemoradiotherapy , Consolidation Chemotherapy , Esophageal Neoplasms/therapy , Esophageal Squamous Cell Carcinoma/therapy , Adult , Aged , Aged, 80 and over , Esophageal Neoplasms/mortality , Esophageal Squamous Cell Carcinoma/mortality , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Metastasis , Prognosis , Progression-Free Survival , Propensity Score , Proportional Hazards Models , Retrospective Studies
3.
Breast Cancer ; 24(3): 345-352, 2017 May.
Article in English | MEDLINE | ID: mdl-28324247

ABSTRACT

To compare the addition of targeted agents to fulvestrant with fulvestrant alone in hormone-receptor positive advanced breast cancer progressed on previous endocrine therapy; a meta-analysis of all relevant randomized controlled trials was performed. The PubMed, Embase databases and the Cochrane Central Register of Controlled Trials were searched for relevant publications reporting randomized controlled trials between January 2000 and June 2016. Progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were assessed. Eight trials with a total of 2,470 patients were included in this meta-analysis. Compared with fulvestrant alone, combination therapy improved PFS (HR = 0.79; 95% CI 0.72-0.87; P = 0.00), increased ORR (RR = 1.70; 95% CI 1.30-2.21; P = 0.00), and showed a trend of increase in DCR (RR = 1.27; 95% CI 0.96-1.69, P = 0.09). In network analysis, only CD4/6 and PI3K/m-TOR inhibitors showed significant treatment effects with a P-score of 0.9999 and 0.7615, respectively. Patients treated with combination therapy developed more grade 3 or greater toxic effects (RR = 1.24; 95% CI 1.13-1.36; P = 0.00). Combining targeted agents with fulvestrant showed benefit but with increased toxicity in patients with advanced breast cancer compared with fulvestrant alone. Biomarkers for treatment optimization are lacking. The CD4/6 and PI3K/m-TOR pathways merit further investigation.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Estradiol/analogs & derivatives , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Disease-Free Survival , Estradiol/administration & dosage , Estradiol/adverse effects , Estradiol/therapeutic use , Female , Fulvestrant , Humans , Molecular Targeted Therapy/methods , Randomized Controlled Trials as Topic , Receptors, Estrogen/metabolism , Treatment Outcome
4.
PLoS One ; 11(10): e0164663, 2016.
Article in English | MEDLINE | ID: mdl-27741288

ABSTRACT

Capecitabine has been investigated in early breast cancer in several studies, but it was undefined that whether it could improve survival. To investigate whether the addition of capecitabine affected survival in patients with early breast cancer, a meta-analysis was conducted and overall survival (OS), disease-free survival (DFS), and toxicity were assessed. The PubMed, Embase databases and the Cochrane Central Register of Controlled Trials were searched for studies between January 2006 and April 2016. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CI were derived. Seven trials with 9097 patients, consisted of 4 adjuvant and 3 neoadjuvant studies, were included in this meta-analysis. Adding capecitabine showed no improvement in DFS (HR = 0.93; 95% CI, 0.85-1.02; P = 0.12), whereas a significant improvement in OS was observed (HR = 0.85; 95% CI, 0.75-0.96; P = 0.008). A sub-analysis of DFS showed that benefit of capecitabine derived from patients with triple negative subtype and with extensive axillary involvement. Safety profiles were consistent with the known side-effects of capecitabine, but more patients discontinued scheduled treatment in the capecitabine group. Combining capecitabine with standard (neo)adjuvant regimens in early breast cancer demonstrated a significantly superior OS, and indicated DFS improvement in some subtypes with high risk of recurrence. Selection of subtypes was a key to identify patients who might gain survival benefit from capecitabine.


Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Capecitabine/therapeutic use , Antineoplastic Agents/adverse effects , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Capecitabine/adverse effects , Chemotherapy, Adjuvant , Databases, Factual , Disease-Free Survival , Female , Humans , Neoplasm Staging , Proportional Hazards Models , Randomized Controlled Trials as Topic , Survival Rate
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