scholarly journals Managing advanced HR-positive, HER2-negative breast cancer with CDK4/6 inhibitors in post-menopausal patients: is there a best sequence?

2018 ◽  
Vol 10 ◽  
pp. 175883591881559 ◽  
Author(s):  
Lorenzo Rossi ◽  
Amelia McCartney ◽  
Emanuela Risi ◽  
Luca Malorni ◽  
Laura Biganzoli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammalian Target Of Rapamycin ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Therapeutic Landscape ◽  
Wide Range ◽  
Epidermal Growth ◽  
Post Menopausal ◽  
Complex Scenario

The current therapeutic landscape of luminal human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC) is fundamentally evolving, particularly in the advent of molecularly targeted therapies, such as inhibitors of mammalian target of rapamycin and cyclin-dependent kinase 4/6 (CDK4/6). In the context of CDK4/6 inhibitors, landmark clinical trials for palbociclib (PALOMA-1, PALOMA-2, PALOMA-3), ribociclib (MONALEESA-2, MONALEESA-3, MONALEESA-7) and abemaciclib (MONARCH-1, MONARCH-2, MONARCH-3) have provided solid data regarding progression-free survival and overall response rate, justifying the introduction of this class of drugs into our therapeutic armoury. However, several clinical questions remain open. One of the most relevant issues faced in practice is that of the optimum sequencing of CDK4/6 inhibitors, particularly given the wide range of therapeutic options open to clinicians treating luminal mBC. In this brief commentary, we would like to focus on the best sequence for CDK4/6 inhibitors and their place in this growing, complex scenario.

scholarly journals Randomized Phase II Trial of Fulvestrant Plus Everolimus or Placebo in Postmenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer Resistant to Aromatase Inhibitor Therapy: Results of PrE0102

2018 ◽  
Vol 36 (16) ◽  
pp. 1556-1563 ◽  
Author(s):  
Noah Kornblum ◽  
Fengmin Zhao ◽  
Judith Manola ◽  
Paula Klein ◽  
Bhuvaneswari Ramaswamy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Objective Response ◽  
Mammalian Target Of Rapamycin ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Free Survival ◽  
Er Positive ◽  
Epidermal Growth

Purpose The mammalian target of rapamycin inhibitor everolimus targets aberrant signaling through the PI3K/AKT/mammalian target of rapamycin pathway, a mechanism of resistance to anti-estrogen therapy in estrogen receptor (ER)–positive breast cancer. We hypothesized that everolimus plus the selective ER downregulator fulvestrant would be more efficacious than fulvestrant alone in ER-positive metastatic breast cancer resistant to aromatase inhibitor (AI) therapy. Patients and Methods This randomized, double-blind, placebo-controlled, phase II study included 131 postmenopausal women with ER-positive, human epidermal growth factor receptor 2–negative, AI-resistant metastatic breast cancer randomly assigned to fulvestrant (500 mg days 1 and 15 of cycle 1, then day 1 of cycles 2 and beyond) plus everolimus or placebo. The study was designed to have 90% power to detect a 70% improvement in median progression-free survival from 5.4 months to 9.2 months. Secondary end points included objective response and clinical benefit rate (response or stable disease for at least 24 weeks). Prophylactic corticosteroid mouth rinses were not used. Results The addition of everolimus to fulvestrant improved the median progression-free survival from 5.1 to 10.3 months (hazard ratio, 0.61 [95% CI, 0.40 to 0.92]; stratified log-rank P = .02), indicating that the primary trial end point was met. Objective response rates were similar (18.2% v 12.3%; P = .47), but the clinical benefit rate was significantly higher in the everolimus arm (63.6% v 41.5%; P = .01). Adverse events of all grades occurred more often in the everolimus arm, including oral mucositis (53% v 12%), fatigue (42% v 22%), rash (38% v 5%), anemia (31% v. 6%), diarrhea (23% v 8%), hyperglycemia (19% v 5%), hypertriglyceridemia (17% v 3%), and pneumonitis (17% v 0%), although grade 3 to 4 events were uncommon. Conclusion Everolimus enhances the efficacy of fulvestrant in AI-resistant, ER-positive metastatic breast cancer.

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).

scholarly journals Systemic control and encephalic response with lapatinib plus capecitabine as second-line therapy in HER2-positive, metastatic breast cancer

ABOUTOPEN ◽  
2018 ◽  
Vol 4 (1) ◽  
pp. 110-115
Author(s):  
Raffaele Ardito ◽  
Fiorella Restaino Marino
Keyword(s):  
Breast Cancer ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Second Line ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Free Survival ◽  
Systemic Control ◽  
Epidermal Growth

Overexpression of the human epidermal growth factor receptor (HER2) oncoprotein in breast cancer patients, is one of the biological characteristics of the disease that determines the choice of appropriate systemic treatment. We report the case of a 41-year-old woman, with relapsing HER2-positive breast cancer in cerebral and pulmonary cells. The patient underwent multimodal first Iine treatment including pertuzumab, trastuzumab and docetaxel and panencephalic radiotherapy with good response and progression-free survival for approximately 16 months. Subsequently, further to a encephalic progression of the disease, the patient was treated in second line with the combination lapatinib + capecitabine which induced further encephalic response and disease control for additional 20 months (Oncology).

scholarly journals Trastuzumab and fulvestrant combination therapy for women with advanced breast cancer positive for hormone receptor and human epidermal growth factor receptor 2: a retrospective single-center study

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Yukinori Ozaki ◽  
Yosuke Aoyama ◽  
Jun Masuda ◽  
Lina Inagaki ◽  
Saori Kawai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Combination Therapy ◽  
Hormone Receptor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Her2 Positive ◽  
Free Survival ◽  
Epidermal Growth

Abstract Background Trastuzumab and fulvestrant combination therapy is one of the treatment options for patients with hormone receptor- and human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer; however, there are limited studies evaluating the efficacy of this combination therapy. Methods We retrospectively reviewed the data of women with hormone receptor- and HER2-positive metastatic breast cancer who received trastuzumab and fulvestrant combination therapy between August 1997 and August 2020 at the Cancer Institute Hospital. The primary endpoint of this study was progression-free survival, and the secondary endpoints were response rate, overall survival and safety. Results We reviewed the data of 1612 patients with recurrent or metastatic breast cancer, of which 118 patients were diagnosed with hormone receptor- and HER2-positive breast cancer. Of these, 28 patients who received trastuzumab and fulvestrant combination therapy were eligible for this study. The median treatment line for advanced breast cancer was 6 (range, 1–14), the median progression-free survival was 6.4 months (95% confidence interval [CI], 3.46–8.17), and the median overall survival was 35.3 months (95% CI, 20.0–46.7). Of the 28 patients, partial response was observed in 1 (4%), stable disease in 17 (61%), and progressive disease in 10 (36%) patients. The disease control rate was 64%. Adverse events of grade ≥ 3 were not observed. Conclusions Trastuzumab and fulvestrant combination therapy showed moderate clinical efficacy and no severe toxicity after standard anti-HER2 treatment, which is a reasonable treatment option for patients with hormone receptor- and HER2-positive metastatic breast cancer. These data contribute to understanding the efficacy of trastuzumab and fulvestrant combination therapy as control data for further development of anti-HER2 agents plus hormone therapy.

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