scholarly journals Updates on managing advanced breast cancer with palbociclib combination therapy

2018 ◽  
Vol 10 ◽  
pp. 175883591879384 ◽  
Author(s):  
Teresa M. McShane ◽  
Thomas A. Wolfe ◽  
Joanne C. Ryan
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Metastatic Breast ◽  
Clinical Trial Data ◽  
Progression Free Survival ◽  
Advanced Breast ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Patient Reported ◽  
Subgroup Analyses

Background: The objective of this study was to review the pharmacology, efficacy, and safety of palbociclib, a first-in-class cyclin-dependent kinase 4/6 inhibitor, for the management of advanced breast cancer (ABC). Methods: Pharmacokinetics and drug interactions associated with palbociclib are described. Recent clinical trial data are reviewed, including patient-reported outcomes and subgroup analyses. Results: Palbociclib is indicated in combination with an aromatase inhibitor as initial endocrine therapy (ET) or with fulvestrant for patients with disease progression following ET for hormone receptor positive, human epidermal growth factor receptor 2 negative ABC or metastatic breast cancer. Palbociclib inhibits cyclin-dependent kinases 4/6, resulting in a blockade of phosphorylation of the retinoblastoma protein, which hinders the activation of transcription factors involved in S-phase entry, thereby arresting cell cycle progression at G1 phase. The efficacy and safety of palbociclib in combination with ET was established in three randomized trials (PALOMA-1, -2, and -3); all studies met their primary endpoint of significantly prolonging investigator-assessed progression-free survival versus ET alone. Findings were similar in subgroup analyses of the three PALOMA studies. Palbociclib plus ET also maintained health-related quality of life (QoL) compared with ET alone in PALOMA-2 and -3. A long-term safety profile for palbociclib, up to 3 years, has been established. Neutropenia, the most common any-grade and grade 3 or higher adverse event associated with palbociclib, is consistent with the drug’s mechanism of action and can be effectively managed with dose interruption, dose reduction, or delay in starting treatment cycles. Conclusions: Palbociclib in combination with ET improved progression-free survival and QoL in patients with ABC, including in several patient subgroups.

scholarly journals Deep exploration of PARP inhibitors in breast cancer: monotherapy and combination therapy

2021 ◽  
Vol 49 (2) ◽  
pp. 030006052199101
Author(s):  
Zheling Chen ◽  
Xiao Wang ◽  
Xiao Li ◽  
Yucheng Zhou ◽  
Ke Chen
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Meta Analysis ◽  
Treatment Options ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Advanced Breast ◽  
Systemic Review ◽  
Brca Mutations ◽  
Free Survival

Objective Nearly 5% of patients with breast cancer carry germline BRCA mutations, which are more common in triple-negative breast cancer (TNBC). Previous clinical trials demonstrated the therapeutic efficacy of poly (ADP-ribose) polymerase inhibitors (PARPis) against BRCA-mutated metastatic breast cancer. The current study conducted a systemic review and meta-analysis of the clinical efficiency and safety of PARPis, either alone or combined with chemotherapy, in patients with TNBC. Methods We searched PubMed, EMBASE, and ClinicalTrials.gov to identify randomized controlled trials comparing PARPi therapy with chemotherapy, and comparisons of chemotherapy plus PARPis with chemotherapy alone were included. The study endpoints included the clinical response, progression-free survival, and adverse event rates. Results PARPi therapy was revealed to improve progression-free survival in patients with advanced breast cancer, either alone or in combination with chemotherapy. Subgroup analysis illustrated that patients with mutant BRCA1 and mutant BRCA2 and those who had not been treated with platinum-based agents could specifically benefit from PARPis. Conclusion PARPi monotherapy can significantly improve clinical outcomes in patients with advanced breast cancer, especially those with TNBC, those who had not previously received platinum therapy, and those with mutant BRCA1/2. PARPis combined with chemotherapy represent new treatment options for patients with advanced cancer.

scholarly journals Progression-free survival as a surrogate endpoint in advanced breast cancer

2008 ◽  
Vol 24 (04) ◽  
pp. 371-383 ◽  
Author(s):  
Rebecca A. Miksad ◽  
Vera Zietemann ◽  
Raffaella Gothe ◽  
Ruth Schwarzer ◽  
Annette Conrads-Frank ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Treatment Effect ◽  
Cross Validation ◽  
Progression Free Survival ◽  
Kappa Statistic ◽  
Surrogate Endpoint ◽  
Advanced Breast ◽  
Free Survival ◽  
Subgroup Analyses

Objectives:Progression-free survival (PFS) has not been validated as a surrogate endpoint for overall survival (OS) for anthracycline (A) and taxane-based (T) chemotherapy in advanced breast cancer (ABC). Using trial-level, meta-analytic approaches, we evaluated PFS as a surrogate endpoint.Methods:A literature review identified randomized, controlled A and T trials for ABC. Progression-based endpoints were classified by prospective definitions. Treatment effects were derived as hazard ratios for PFS (HRPFS) and OS (HROS). Kappa statistic assessed overall agreement. A fixed-effects regression model was used to predict HROSfrom observed HRPFS. Cross-validation was performed. Sensitivity and subgroup analyses were performed for PFS definition, year of last patient recruitment, line of treatment, and constant rate assumption.Results:Sixteen A and fifteen T trials met inclusion criteria, producing seventeen A (n= 4,323) and seventeen T (n= 5,893) trial-arm pairs. Agreement (kappa statistic) between the direction of HROSand HRPFSwas 0.71 for A (p= .0029) and 0.75 for T (p= .0028). While HRPFSwas a statistically significant predictor of HROSfor both A (p= .0019) and T (p= .012), the explained variances were 0.49 (A) and 0.35 (T). In cross-validation, 97 percent of the 95 percent prediction intervals crossed the equivalence line, and the direction of predicted HROSagreed with observed HROSin 82 percent (A) and 76 percent (T). Results were robust in sensitivity and subgroup analyses.Conclusions:This meta-analysis suggests that the trial-level treatment effect on PFS is significantly associated with the trial-level treatment effect on OS. However, prediction of OS based on PFS is surrounded with uncertainty.

scholarly journals Implementation and Feasibility of Electronic Patient-Reported Outcome (ePRO) Data Entry in the PRAEGNANT Real-Time Advanced and Metastatic Breast Cancer Registry

2017 ◽  
Vol 77 (08) ◽  
pp. 870-878 ◽  
Author(s):  
Markus Wallwiener ◽  
Felix Heindl ◽  
Sara Brucker ◽  
Florin-Andrei Taran ◽  
Andreas Hartkopf ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Advanced Breast Cancer ◽  
Cancer Registry ◽  
Data Entry ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Patient Reported ◽  
Trial Staff ◽  
Breast Cancer Registry

Abstract Purpose Patient-reported outcomes (PROs) have been incorporated into clinical trials for many symptoms and medical conditions. A transition from paper-based capture of PROs to electronic PROs (ePROs) has recently started. This study reports on the feasibility of ePRO assessment in a prospective registry including molecular data for patients with advanced breast cancer. Methods As part of the PRAEGNANT network, patients were invited by clinical trial staff, physicians, and nurses to complete three standardized Internet-based questionnaires (EQ 5D 5 L, CES-D and IPAQ). Feasibility was assessed by the staff members who assigned the user accounts by the patients. The completeness of the questionnaires was also assessed. Results Fifteen of 17 patients who were asked agreed to participate to complete the PRO questionnaires (EQ-5D-5L and CES-D). However, the IPAQ (physical activity) questionnaire was only validly completed by 9 patients. Feasibility was ranked better by the physicians and dedicated clinical trial staff than by the nursing staff. Conclusions Incorporating ePRO questionnaires into an advanced breast cancer registry is feasible, and no major hurdles were reported. Involving stakeholders from the start, the application is tailored to the capacities and abilities of both patients and clinical staff. The patientsʼ compliance was better with some questionnaires, but others may present difficulties.

AMEERA-5: A randomized, double-blind phase III study of amcenestrant (SAR439859) + palbociclib versus letrozole + palbociclib for previously untreated ER+/HER2- advanced breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS1104-TPS1104
Author(s):  
Aditya Bardia ◽  
Javier Cortes ◽  
Sara A. Hurvitz ◽  
Suzette Delaloge ◽  
Hiroji Iwata ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Phase I ◽  
Advanced Breast Cancer ◽  
Progression Free Survival ◽  
Advanced Breast ◽  
Phase Iii ◽  
Double Blind ◽  
Free Survival ◽  
Phase Iii Study

TPS1104 Background: Selective estrogen receptor degraders (SERDs) block estrogen receptor (ER) associated signaling and have created interest for treating patients (pts) with advanced ER+ breast cancer (BC). Fulvestrant is currently the only SERD available for advanced BC but requires intramuscular administration, limiting the applied dose, exposure and receptor engagement. Amcenestrant (SAR439859) is an oral SERD that binds with high affinity to both wild-type and mutant ER, blocking estradiol binding and promoting up to 98% ER degradation in preclinical studies. In the phase I AMEERA-1 study of pretreated pts with ER+/HER2- advanced BC, amcenestrant 150–600 mg once daily (QD) showed a mean ER occupancy of 94% with plasma concentrations > 100 ng/mL and a favorable safety profile (Bardia, 2019; data on file). Combination therapy with amcenestrant + palbociclib (palbo) was also evaluated as part of this ongoing phase I study. CDK 4/6 inhibitors (CDK4/6i) combined with an aromatase inhibitor (AI), the gold standard for first line treatment for advanced breast cancer, prolong progression free survival (PFS) in pts with no prior treatment for ER+/HER2- advanced BC, but OS benefit has not been shown yet in postmenopausal pts. There remains a clinical need for more effective treatments in this setting. Methods: AMEERA-5 (NCT04478266) is an ongoing, prospective, randomized, double-blind phase III study comparing the efficacy and safety of amcenestrant + palbo with that of letrozole + palbo in pts with advanced, locoregional recurrent or metastatic ER+/HER2- BC who have not received prior systemic therapy for advanced disease. The study includes men, pre/peri-menopausal (with goserelin) and post-menopausal women. Pts with progression during or within 12 months of (neo)adjuvant endocrine therapy using any of the following agents are excluded: AI, selective estrogen receptor modulators, CDK4/6i. Pts are randomized 1:1 to either continuous amcenestrant 200 mg or letrozole 2.5 mg QD orally with matching placebos; both combined with palbo 125 mg QD orally (d1–21 every 28-d cycle). Randomization is stratified according to disease type (de novo metastatic vs recurrent disease), the presence of visceral metastasis, and menopausal status. The primary endpoint is investigator assessed progression free survival (PFS) (RECIST v1.1). Secondary endpoints are overall survival, PFS2, objective response rate, duration of response, clinical benefit rate, pharmacokinetics of amcenestrant and palbo, health-related quality of life, time to chemotherapy, and safety. Biomarkers will be measured in paired tumor biopsies and cell free deoxyribonucleic acid (cfDNA) over time. Target enrolment = 1066 pts; enrolment as of 1/2021 = 33 pts. Bardia A, et al., J Clin Oncol. 2019; 37 (15 suppl):1054 Clinical trial information: NCT04478266 .

scholarly journals Peripheral cytotoxic T lymphocyte predicts first-line progression free survival in HER2-positive advanced breast cancer

The Breast ◽  
2021 ◽  
Vol 55 ◽  
pp. 7-15
Author(s):  
Xiao-Ran Liu ◽  
Jian-Jun Yu ◽  
Guo-Hong Song ◽  
Li-Jun Di ◽  
Han-Fang Jiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Progression Free Survival ◽  
Advanced Breast ◽  
First Line ◽  
Her2 Positive ◽  
Free Survival

scholarly journals MONALEESA clinical program: a review of ribociclib use in different clinical settings

2019 ◽  
Vol 15 (23) ◽  
pp. 2673-2686 ◽  
Author(s):  
Denise A Yardley
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Ovarian Function ◽  
Progression Free Survival ◽  
Advanced Breast ◽  
Free Survival ◽  
Ovarian Function Suppression ◽  
First Line Therapy ◽  
Clinical Program ◽  
Treatment Naïve

Ribociclib has received approval in the pre/peri- and postmenopausal disease settings on the basis of the MONALEESA trials. MONALEESA-2 demonstrated that ribociclib plus letrozole significantly improved progression-free survival compared with placebo plus letrozole as first-line therapy in postmenopausal patients with HR-positive, HER2-negative advanced breast cancer. Subsequently, ongoing trials reported significant progression-free survival improvements with ribociclib in combination with either fulvestrant in postmenopausal patients with advanced breast cancer who were either treatment naive or received ≤1 line of prior endocrine therapy in the advanced disease setting (MONALEESA-3) or tamoxifen/nonsteroidal aromatase inhibitor with ovarian function suppression in pre/perimenopausal women (MONALEESA-7). This review summarizes the MONALEESA clinical program. ClinicalTrials.gov identifiers: NCT01958021 (MONALEESA-2), NCT02422615 (MONALEESA-3), NCT02278120 (MONALEESA-7).

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