scholarly journals PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy—Safety and Efficacy in Asian Patients

2017 ◽  
Vol 3 (4) ◽  
pp. 289-303 ◽  
Author(s):  
Hiroji Iwata ◽  
Seock-Ah Im ◽  
Norikazu Masuda ◽  
Young-Hyuck Im ◽  
Kenichi Inoue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Asian Patients ◽  
Hormone Receptor Positive ◽  
Patient Reported ◽  
Epidermal Growth

Purpose To assess efficacy and safety of palbociclib plus fulvestrant in Asians with endocrine therapy–resistant metastatic breast cancer. Patients and Methods The Palbociclib Ongoing Trials in the Management of Breast Cancer 3 (PALOMA-3) trial, a double-blind phase III study, included 521 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer with disease progression on endocrine therapy. Patient-reported outcomes (PROs) were assessed on study treatment and at the end of treatment. Results This preplanned subgroup analysis of the PALOMA-3 study included premenopausal and postmenopausal Asians taking palbociclib plus fulvestrant (n = 71) or placebo plus fulvestrant (n = 31). Palbociclib plus fulvestrant improved progression-free survival (PFS) compared with fulvestrant alone. Median PFS was not reached with palbociclib plus fulvestrant (95% CI, 9.2 months to not reached) but was 5.8 months with placebo plus fulvestrant (95% CI, 3.5 to 9.2 months; hazard ratio, 0.485; 95% CI, 0.270 to 0.869; P = .0065). The most common all-cause grade 3 or 4 adverse events in the palbociclib arm were neutropenia (92%) and leukopenia (29%); febrile neutropenia occurred in 4.1% of patients. Within-patient mean trough concentration comparisons across subgroups indicated similar palbociclib exposure between Asians and non-Asians. Global quality of life was maintained; no statistically significant changes from baseline were observed for patient-reported outcome scores with palbociclib plus fulvestrant. Conclusion This is the first report, to our knowledge, showing that palbociclib plus fulvestrant improves PFS in asian patients. Palbociclib plus fulvestrant was well tolerated in this study.

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.

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.

Fulvestrant ('Faslodex')--a new treatment option for patients progressing on prior endocrine therapy.

2002 ◽  
pp. 267-276 ◽  
Author(s):  
C Morris ◽  
A Wakeling
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Metastatic Breast Cancer ◽  
Advanced Breast Cancer ◽  
Postmenopausal Women ◽  
Endocrine Therapy ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Phase Iii ◽  
Hormone Receptor Positive

Since its introduction more than 30 years ago, tamoxifen has been the most widely used endocrine therapy for the treatment of women with advanced breast cancer. More recently, a number of alternative endocrine treatments have been developed, including several selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs) and, most recently, fulvestrant ('Faslodex'). Fulvestrant is an estrogen receptor (ER) antagonist, which, unlike the SERMs, has no known agonist (estrogenic) effect and downregulates the ER protein. Tamoxifen is effective and well tolerated, although the non-steroidal AIs, anastrozole and letrozole, are more effective treatments for advanced disease than tamoxifen. Fulvestrant has recently gained US Food and Drug Administration approval for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. In two global phase III clinical trials fulvestrant was at least as effective and as equally well tolerated as anastrozole for the treatment of postmenopausal women with advanced and metastatic breast cancer. In a retrospective analysis of the combined data from these trials, mean duration of response was significantly greater for fulvestrant compared with anastrozole. These new hormonal treatments expand the choice of endocrine therapy for women with advanced breast cancer and offer new options for sequencing and combining treatments.

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