Introduction: The efficacy of neoadjuvant buparlisib for breast cancer remains controversial. We conduct a systematic review and meta-analysis to explore the influence of neoadjuvant buparlisib versus placebo for breast cancer.
Methods: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through May 2019 for randomized controlled trials (RCTs) assessing the efficacy and safety of neoadjuvant buparlisib versus placebo for breast cancer. This meta-analysis is performed using the random-effect model.
Results: Four RCTs are included in the meta-analysis. Overall, compared with control group for breast cancer, neoadjuvant buparlisib can substantially reduce progressive disease (risk ratios [RR] = 0.66; 95% confidence interval [CI] = 0.52-0.82; P = .0003) and improve stable disease (RR = 1.29; 95% CI = 1.02-1.64; P = .04), but has no notable influence on overall response rate (RR = 1.32; 95% CI = 0.84-2.06; P = .22), clinical benefit rate (RR = 1.06; 95% CI = 0.79-1.43; P = .69). Neoadjuvant buparlisib results in the increase in adverse grade 3/4 adverse events including increased alanine aminotransferase (ALT) (RR = 11.87; 95% CI = 5.65-24.90; P < .00001), increased aspartate aminotransferase (AST) (RR = 6.50; 95% CI = 4.14-10.21; P < .00001) and hyperglycaemia (RR = 36.65; 95% CI = 10.44-128.68; P < .00001), as well as serious adverse events (RR = 1.47; 95% CI = 1.23-1.76; P < .0001) compared to placebo. Deaths is found to be similar between two groups (RR = 0.88; 95% CI = 0.75-1.04; P = .13).
Conclusions: Neoadjuvant buparlisib may provide some efficacy for breast cancer, but leads to the increase in serious adverse events.
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http://dx.doi.org/10.1097/MD.0000000000017614 | DOI Listing |
Clin Cancer Res
November 2022
Harvard Medical School, Department of Medicine, Boston, Massachusetts.
Purpose: The identification of patients with homologous recombination deficiency (HRD) beyond BRCA1/2 mutations is an urgent task, as they may benefit from PARP inhibitors. We have previously developed a method to detect mutational signature 3 (Sig3), termed SigMA, associated with HRD from clinical panel sequencing data, that is able to reliably detect HRD from the limited sequencing data derived from gene-focused panel sequencing.
Experimental Design: We apply this method to patients from two independent datasets: (i) high-grade serous ovarian cancer and triple-negative breast cancer (TNBC) from a phase Ib trial of the PARP inhibitor olaparib in combination with the PI3K inhibitor buparlisib (BKM120; NCT01623349), and (ii) TNBC patients who received neoadjuvant olaparib in the phase II PETREMAC trial (NCT02624973).
Medicine (Baltimore)
November 2019
Department of Radiation Oncology, Chongqing Cancer Institute & Hospital & Cancer Center.
Introduction: The efficacy of neoadjuvant buparlisib for breast cancer remains controversial. We conduct a systematic review and meta-analysis to explore the influence of neoadjuvant buparlisib versus placebo for breast cancer.
Methods: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through May 2019 for randomized controlled trials (RCTs) assessing the efficacy and safety of neoadjuvant buparlisib versus placebo for breast cancer.
Purpose: Phosphatidylinositol 3-kinase (PI3K) signaling is highly active in glioblastomas. We assessed pharmacokinetics, pharmacodynamics, and efficacy of the pan-PI3K inhibitor buparlisib in patients with recurrent glioblastoma with PI3K pathway activation.
Methods: This study was a multicenter, open-label, multi-arm, phase II trial in patients with PI3K pathway-activated glioblastoma at first or second recurrence.
Eur J Cancer
November 2017
Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Australian New Zealand Breast Cancer Trials Group (ANZBCTG), Newcastle, Australia. Electronic address:
Aim: The Neoadjuvant PI3K inhibition in HER2 OverExpressing Breast cancEr (NeoPHOEBE) trial evaluated the efficacy and safety of buparlisib, a pan-phosphatidylinositol 3-kinase (PI3K) inhibitor, plus trastuzumab and paclitaxel as neoadjuvant treatment for human epidermal growth factor receptor-2 positive (HER2+) breast cancer.
Methods: NeoPHOEBE was a neoadjuvant, phase II, randomised, double-blind study. Women with HER2+ breast cancer were randomised within two independent cohorts by PIK3CA mutation status and, in each cohort stratified by oestrogen receptor (ER) status to receive buparlisib or placebo plus trastuzumab (first 6 weeks) followed by buparlisib or placebo with trastuzumab and paclitaxel.
Cancer Res
June 2017
Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.
mutations are associated with resistance to HER2-targeted therapies. We previously showed that transgenic mammary tumors are resistant to the HER2 antibodies trastuzumab and pertuzumab but respond to PI3K inhibitor buparlisib (TPB). In this study, we identified mechanisms of resistance to combined inhibition of HER2 and PI3K.
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