Alpelisib in the treatment of metastatic HR+ breast cancer with PIK3CA mutations

2020 ◽  
Author(s):  
Athanasios Mavratzas ◽  
Frederik Marmé
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Hormone Receptor ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Endocrine Treatment ◽  
Pik3ca Mutations ◽  
Hormone Receptor Positive ◽  
Fda Approval

Since the US FDA approval of everolimus/exemestane in July 2012, and of the first CDK 4/6 inhibitor, palbociclib, combined with endocrine treatment in February 2015, a third class of therapeutic compounds, the PI3K inhibitors, has been introduced to the arsenal of targeted therapies overcoming endocrine resistance in hormone receptor-positive metastatic breast cancer. Alpelisib (PIQRAY®) is the first of these novel agents yielding promising clinical results, giving an impetus to further development of tailored endocrine anticancer treatments. Herein, we review its pharmacodynamic and pharmacokinetic properties, safety and efficacy data, as well as Phase III SOLAR-1 trial, prompting FDA approval of alpelisib in hormone receptor-positive metastatic breast cancer harboring PIK3CA mutations. Furthermore, implications for clinical use and current research will also be discussed.

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 CDK4/6 Inhibitors in Hormone Receptor-Positive Metastatic Breast Cancer: Current Practice and Knowledge

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2480
Author(s):  
Debora de Melo Gagliato ◽  
Antonio C Buzaid ◽  
Jose Manuel Perez-Garcia ◽  
Antonio Llombart ◽  
Javier Cortes
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Hormone Receptor ◽  
Current Knowledge ◽  
Metastatic Breast ◽  
Endocrine Treatment ◽  
Cyclin Dependent Kinase ◽  
Hormone Receptor Positive ◽  
Positive Breast Cancer

Treatment paradigms in advanced hormone receptor (HR)-positive breast cancer were substantially transformed with cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) approval. The addition of these drugs to endocrine treatment profoundly improved progression-free and overall survival. Additionally, other important endpoints, such as the response rate, time to chemotherapy, and a delay in quality of life deterioration, were positively impacted by CDK4/6 inhibitors’ addition to the treatment of advanced HR-positive breast cancer. This review article will summarize current knowledge on CDK4/6 inhibitors in clinical practice for advanced HR-positive metastatic breast cancer, as well as describe recent efforts to more precisely characterize mechanisms of sensitivity and resistance to these drugs, both on the molecular and clinical characterization level.

Trastuzumab Plus Anastrozole Versus Anastrozole Alone for the Treatment of Postmenopausal Women With Human Epidermal Growth Factor Receptor 2–Positive, Hormone Receptor–Positive Metastatic Breast Cancer: Results From the Randomized Phase III TAnDEM Study

2009 ◽  
Vol 27 (33) ◽  
pp. 5529-5537 ◽  
Author(s):  
Bella Kaufman ◽  
John R. Mackey ◽  
Michael R. Clemens ◽  
Poonamalle P. Bapsy ◽  
Ashok Vaid ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Metastatic Breast Cancer ◽  
Adverse Events ◽  
Hormone Receptor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Hormone Receptor Positive ◽  
Epidermal Growth

Purpose TAnDEM is the first randomized phase III study to combine a hormonal agent and trastuzumab without chemotherapy as treatment for human epidermal growth factor receptor 2 (HER2)/hormone receptor–copositive metastatic breast cancer (MBC). Patients and Methods Postmenopausal women with HER2/hormone receptor–copositive MBC were randomly assigned to anastrozole (1 mg/d orally) with or without trastuzumab (4 mg/kg intravenous infusion on day 1, then 2 mg/kg every week) until progression. The primary end point was progression-free survival (PFS) in the intent-to-treat population. Results Overall, 103 patients received trastuzumab plus anastrozole; 104 received anastrozole alone. Patients in the trastuzumab plus anastrozole arm experienced significant improvements in PFS compared with patients receiving anastrozole alone (hazard ratio = 0.63; 95% CI, 0.47 to 0.84; median PFS, 4.8 v 2.4 months; log-rank P = .0016). In patients with centrally confirmed hormone receptor positivity (n = 150), median PFS was 5.6 and 3.8 months in the trastuzumab plus anastrozole and anastrozole alone arms, respectively (log-rank P = .006). Overall survival in the overall and centrally confirmed hormone receptor–positive populations showed no statistically significant treatment difference; however, 70% of patients in the anastrozole alone arm crossed over to receive trastuzumab after progression on anastrozole alone. Incidence of grade 3 and 4 adverse events was 23% and 5%, respectively, in the trastuzumab plus anastrozole arm, and 15% and 1%, respectively, in the anastrozole alone arm; one patient in the combination arm experienced New York Heart Association class II congestive heart failure. Conclusion Trastuzumab plus anastrozole improves outcomes for patients with HER2/hormone receptor–copositive MBC compared with anastrozole alone, although adverse events and serious adverse events were more frequent with the combination.

scholarly journals Hormone receptor–positive, HER2-negative metastatic breast cancer: redrawing the lines

2018 ◽  
Vol 25 ◽  
pp. 131 ◽  
Author(s):  
A. Matutino ◽  
A.A. Joy ◽  
C. Brezden-Masley ◽  
S. Chia ◽  
S. Verma
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Benefit ◽  
Hormone Receptor ◽  
Single Agent ◽  
Treatment Algorithm ◽  
Metastatic Breast ◽  
Standards Of Care ◽  
Endocrine Treatment ◽  
Hormone Receptor Positive

Estrogen receptor modulators and estrogen deprivation have become standards of care for hormone receptor– positive metastatic breast cancer. However, after traditional first-line endocrine monotherapy treatment, the disease typically progresses despite the initial high rate of clinical benefit. Multiple studies have aimed at optimizing treatment strategies to improve upon clinical benefit beyond the traditional single-agent endocrine treatment. With the availability of new data and novel therapies, the clinical practice challenge becomes how best to define the optimal treatment sequence to maximize clinical benefit. In this review, we present treatment options clinically relevant to the management of hormone-positive, her2-negative metastatic breast cancer, and we propose a treatment algorithm based on the current literature.

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