scholarly journals Management of hormone-receptor positive human epidermal receptor 2 negative advanced or metastatic breast cancers

2018 ◽  
Vol 6 (14) ◽  
pp. 284-284 ◽  
Author(s):  
Roger K. C. Ngan
Keyword(s):  
Hormone Receptor ◽  
Metastatic Breast ◽  
Breast Cancers ◽  
Hormone Receptor Positive ◽  
Human Epidermal Receptor

scholarly journals CDK4/6 inhibitors in breast cancer: beyond hormone receptor-positive HER2-negative disease

2018 ◽  
Vol 10 ◽  
pp. 175883591881834 ◽  
Author(s):  
Adriana Matutino ◽  
Carla Amaro ◽  
Sunil Verma
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancers ◽  
Cyclin Dependent Kinase ◽  
Her2 Positive ◽  
Hormone Receptor Positive ◽  
Epidermal Growth

The development of cyclin-dependent kinase (CDK) 4/6 inhibitors has been more prominent in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancers, with a significant improvement in progression-free survival (PFS) in first and later lines of metastatic breast cancer (MBC) therapy. Preclinical evidence suggests that there is activity of CDK4/6 inhibitors in nonluminal cell lines. Here, we present a review of the current preclinical and clinical data on the use of CDK inhibitors in HER2-positive and triple-negative breast cancer (TNBC).

The introduction of a third CDK4/6 inhibitor does not change the cost-effectiveness profile in first and subsequent-lines after progression or relapse during previous endocrine therapy in patients with hormone receptor positive (HR+)/human epidermal receptor-2 negative (HER-2) advanced or metastatic breast cancer

2020 ◽  
Vol 26 (6) ◽  
pp. 1486-1491
Author(s):  
Jacopo Giuliani ◽  
Andrea Bonetti
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Dose Reduction ◽  
Endocrine Therapy ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Full Dose ◽  
Hormone Receptor Positive ◽  
Human Epidermal Receptor

The aim of this study was to assess the pharmacological costs of CDK4/6-inhibitors (palbociclib, ribociclib and abemaciclib) in hormone receptor positive (HR+)/human epidermal receptor 2-negative (HER2-) advanced or metastatic breast cancer (BC). We have considered pivotal phase III randomized controlled trials (RCTs) of palbociclib, ribociclib and abemaciclib for the treatment of postmenopausal women with HR+/HER2- advanced or metastatic BC in first-line in association with letrozole or anastrozole (scenario 1) and in subsequent-lines after progression or relapse during previous endocrine therapy (scenario 2).The costs of drugs are at the Pharmacy of our Hospital and are expressed in euros (€). Six phase III RCTs, including 3843 patients, were considered. In the scenario 1, abemaciclib resulted the less expensive at the full dose, with 2246 € per month of progression free survival (PFS)-gained. Overall ribociclib resulted the less expensive considering the reduction in dosage (36.1% in MONALEESA-2 trial versus (vs). 36.0% of palbociclib in PALOMA-2 trial vs. 43.4% of abemaciclib in MONARCH-3 trial). The price was the same for palbociclib and abemaciclib both at full and with dose reduction. In the scenario 2, the situation was similar to the scenario 1, but with lowest costs for ribociclib per month PFS-gained both at full dose (2070 €) and at dose reduction (1391 € and 690 € at 400 mg and 200 mg, respectively). Combining pharmacological costs of drugs with the measure of efficacy represented by the PFS, ribociclib was the less expensive in both scenarios.

scholarly journals Clinical implications of drug-screening assay for recurrent metastatic hormone receptor-positive, human epidermal receptor 2-negative breast cancer using conditionally reprogrammed cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Rei Mimoto ◽  
Satomi Yogosawa ◽  
Hiroki Saijo ◽  
Atsushi Fushimi ◽  
Hiroko Nogi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Screening ◽  
Hormone Receptor ◽  
Drug Sensitivity ◽  
Cultured Cells ◽  
Metastatic Breast ◽  
New Drugs ◽  
Hormone Receptor Positive ◽  
Her2 Breast Cancer ◽  
Human Epidermal Receptor

Abstract Various new drugs have been developed for treating recurrent hormone receptor-positive (HR+)/human epidermal receptor 2-negative (HER2−) breast cancer. However, directly identifying effective drugs remains difficult. In this study, we elucidated the clinical relevance of cultured cells derived from patients with recurrent HR+/HER2− metastatic breast cancer. The recently established conditionally reprogrammed (CR) cell system enables us to examine heterogeneity, drug sensitivity and cell function using patient-derived tumour samples. The results of microarray analysis, DNA target sequencing and xenograft experiments indicated that the mutation status and pathological features were preserved in CR cells, whereas RNA expression was different from that in the primary tumour cells, especially with respect to cell adhesion-associated pathways. The results of drug sensitivity assays involving the use of primary breast cancer CR cells were consistent with gene expression profiling test data. We performed drug-screening assays using liver metastases, which were sensitive to 66 drugs. Importantly, the result reflected the actual clinical course of this patient. These results supported the use of CR cells obtained from the metastatic lesions of patients with HR+/HER2− breast cancer for predicting the clinical drug efficacy.

scholarly journals Ribociclib and Abemaciclib: CDK4/6 Inhibitors for the Treatment of Hormone Receptor–Positive Metastatic Breast Cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kristina F. Byers, PharmD, BCOP
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Hormone Receptor ◽  
Oral Treatment ◽  
Treatment Options ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Breast Cancers ◽  
Cancer Data ◽  
Hormone Receptor Positive

The treatment landscape of hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) metastatic breast cancer has been modernized by the identification of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. Because the majority of HR+ breast cancers will develop resistance to endocrine therapies (tamoxifen and aromatase inhibitors), newer treatment options are necessary to restore endocrine sensitivity and prolong survival. Ribociclib and abemaciclib are two of three CDK4/6 inhibitors currently approved for first- and second-line treatment of HR+/HER2– metastatic breast cancer. Data from large, phase III clinical trials have demonstrated an improvement in both progression-free and overall survival with the addition of ribociclib or abemaciclib to endocrine-based therapy, establishing a new frontline standard of care. Treatment with ribociclib and abemaciclib provide a convenient oral treatment option that is both efficacious and well tolerated.

scholarly journals Ipatasertib plus paclitaxel for PIK3CA/AKT1/PTEN-altered hormone receptor-positive HER2-negative advanced breast cancer: primary results from cohort B of the IPATunity130 randomized phase 3 trial

2021 ◽  
Author(s):  
Nicholas Turner ◽  
Rebecca A. Dent ◽  
Joyce O’Shaughnessy ◽  
Sung-Bae Kim ◽  
Steven J. Isakoff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Objective Response ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Sensory Neuropathy ◽  
Breast Cancers ◽  
Phase 3 ◽  
Double Blind ◽  
Hormone Receptor Positive

Abstract Purpose PI3K/AKT pathway alterations are frequent in hormone receptor-positive (HR+) breast cancers. IPATunity130 Cohort B investigated ipatasertib–paclitaxel in PI3K pathway-mutant HR+ unresectable locally advanced/metastatic breast cancer (aBC). Methods Cohort B of the randomized, double-blind, placebo-controlled, phase 3 IPATunity130 trial enrolled patients with HR+ HER2-negative PIK3CA/AKT1/PTEN-altered measurable aBC who were considered inappropriate for endocrine-based therapy (demonstrated insensitivity to endocrine therapy or visceral crisis) and were candidates for taxane monotherapy. Patients with prior chemotherapy for aBC or relapse < 1 year since (neo)adjuvant chemotherapy were ineligible. Patients were randomized 2:1 to ipatasertib (400 mg, days 1–21) or placebo, plus paclitaxel (80 mg/m2, days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS). Results Overall, 146 patients were randomized to ipatasertib–paclitaxel and 76 to placebo–paclitaxel. In both arms, median investigator-assessed PFS was 9.3 months (hazard ratio, 1.00, 95% CI 0.71–1.40) and the objective response rate was 47%. Median paclitaxel duration was 6.9 versus 8.8 months in the ipatasertib–paclitaxel versus placebo–paclitaxel arms, respectively; median ipatasertib/placebo duration was 8.0 versus 9.1 months, respectively. The most common grade ≥ 3 adverse events were diarrhea (12% with ipatasertib–paclitaxel vs 1% with placebo–paclitaxel), neutrophil count decreased (9% vs 7%), neutropenia (8% vs 9%), peripheral neuropathy (7% vs 3%), peripheral sensory neuropathy (3% vs 5%) and hypertension (1% vs 5%). Conclusion Adding ipatasertib to paclitaxel did not improve efficacy in PIK3CA/AKT1/PTEN-altered HR+ HER2-negative aBC. The ipatasertib–paclitaxel safety profile was consistent with each agent’s known adverse effects. Trial registration NCT03337724.

scholarly journals Patterns of treatment and outcome of palbociclib plus endocrine therapy in hormone receptor-positive/HER2 receptor-negative metastatic breast cancer: a real-world multicentre Italian study

2021 ◽  
Vol 13 ◽  
pp. 175883592098765
Author(s):  
Raffaella Palumbo ◽  
Rosalba Torrisi ◽  
Federico Sottotetti ◽  
Daniele Presti ◽  
Anna Rita Gambaro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Real World ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Her2 Receptor ◽  
Treatment Line ◽  
Hormone Receptor Positive

Background: The CDK4/6 inhibitor palbociclib combined with endocrine therapy (ET) has proven to prolong progression-free survival (PFS) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC). Few data are available regarding the efficacy of such a regimen outside the clinical trials. Patients and methods: This is a multicentre prospective real-world experience aimed at verifying the outcome of palbociclib plus ET in an unselected population of MBC patients. The primary aim was the clinical benefit rate (CBR); secondary aims were the median PFS, overall survival (OS) and safety. Patients received palbociclib plus letrozole 2.5 mg (cohort A) or fulvestrant 500 mg (cohort B). Results: In total, 191 patients (92 in cohort A, 99 in cohort B) were enrolled and treated, and 182 were evaluable for the analysis. Median age was 62 years (range 47–79); 54% had visceral involvement; 28% of patients had previously performed one treatment line (including chemotherapy and ET), 22.6% two lines and 15.9% three. An overall response rate of 34.6% was observed with 11 (6.0%) complete responses and 52 (28.6%) partial responses. Stable disease was achieved by 78 patients (42.9%) with an overall CBR of 59.8%. At a median follow-up of 24 months (range 6–32), median PFS was 13 months without significant differences between the cohorts. When analysed according to treatment line, PFS values were significantly prolonged when palbociclib-based therapy was administered as first-line treatment (14.0 months), to decrease progressively in second and subsequent lines (11.7 and 6.7 months, respectively). Median OS was 25 months, ranging from 28.0 months in 1st line to 18.0 and 13.0 months in 2nd and subsequent lines, respectively. Conclusions: Our data indicate that palbociclib plus ET is active and safe in HR+/HER2− MBC, also suggesting a better performance of the combinations in earlier treatment lines.

scholarly journals Olaparib in hormone receptor-positive, HER2-negative metastatic breast cancer with a somatic BRCA2 mutation

2021 ◽  
Vol 13 ◽  
pp. 175883592110069
Author(s):  
Lee S. Schwartzberg ◽  
Lesli A. Kiedrowski
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Response ◽  
Hormone Receptor ◽  
Brca2 Mutation ◽  
Locally Advanced ◽  
Susceptibility Gene ◽  
Metastatic Breast ◽  
Breast Cancer Susceptibility Gene ◽  
Hormone Receptor Positive

The oral poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib is approved for the treatment of patients with human epidermal growth factor 2-negative (HER2−) metastatic breast cancer (mBC) and a germline breast cancer susceptibility gene (BRCA) mutation who have been treated with chemotherapy. This case report describes a 63-year-old postmenopausal woman with somatic BRCA2-mutated mBC who responded to olaparib treatment following multiple prior lines of therapy. The patient presented in January 2012 with locally advanced, hormone receptor-positive (HR+), HER2− BC which, despite initial response to neoadjuvant chemotherapy, recurred as bone disease in February 2014, and subsequently skin (June 2016) and liver (October 2016) metastases. A comprehensive 592-gene next-generation sequencing panel (Caris Life Sciences), performed on a skin biopsy, detected a pathogenic frameshift mutation in BRCA2 (H3154fs, c.9460delC), which was not identified in a 28-gene hereditary cancer germline analysis (Myriad Genetics, Inc.), and was therefore considered to be a somatic mutation. In January 2017, cell-free DNA (cfDNA) analysis (Guardant Health, Inc.) confirmed the BRCA2 H3154fs mutation in plasma. After several lines of chemotherapy and endocrine therapy, deriving clinical benefit from eribulin and capecitabine, the disease progressed by October 2017, and olaparib (300 mg orally twice daily) was initiated in January 2018. By April 2018, the liver lesions had shrunk by 80% and a >90% response in multiple skin lesions was noted. Clinical response was maintained for 8 months, followed by progression in the skin in September 2018. Biopsy of recurrent lesions revealed a novel BRCA2 mutation, E3152del (c.9455_9457delAGG), predicted to restore the open reading frame and presumably the mechanism of resistance to olaparib. Further likely resistance mutations were noted in subsequent cfDNA analyses. This case demonstrated a clinical response with olaparib as a later-line therapy for HR+, HER2− mBC with a somatic BRCA2 mutation.

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