Palbociclib Ups PFS in HER2−/ER+ Breast Cancer
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Abstract The experimental CDK-inhibitor palbociclib, when combined with the aromatase inhibitor letrozole, significantly extended progression-free survival in women with HER2-/ER+ breast cancer compared with letrozole alone, according to the final results from a phase II clinical trial of the drug.Keywords:
Letrozole
Palbociclib
Aromatase inhibitor
CDK inhibitor
Fulvestrant
Palbociclib
Letrozole
Anastrozole
Aromatase inhibitor
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Palbociclib
Aromatase inhibitor
Letrozole
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Background: We aim to understand whether all patients with hormonal receptor (HR)-positive (+)/human epidermal growth factor receptor-2 (HER2)-negative (−) metastatic breast cancer (MBC) should receive cyclin D-dependent kinase (CDK) 4/6 inhibitor-based therapy as a first-line approach. Methods: A network meta-analysis (NMA) using the Bayesian hierarchical arm-based model, which provides the estimates for various effect sizes, were computed. Results: First-line treatment options in HR+/HER2− MBC, including CDK 4/6 inhibitors combined with aromatase inhibitors (AIs) or fulvestrant (F), showed a significantly longer progression-free survival (PFS) in comparison with AI monotherapy, with a total of 26% progression risk reduction. In the indirect comparison across the three classes of CDK 4/6 inhibitors and F endocrine-based therapies, the first strategy resulted in longer PFS, regardless of specific CDK 4/6 inhibitor (HR: 0.68; 95% CrI: 0.53–0.87 for palbociclib + AI, HR: 0.65; 95% CrI: 0.53–0.79 for ribociclib + AI, HR: 0.63; 95% CrI: 0.47–0.86 for abemaciclib + AI) and patient’s characteristics. Longer PFS was also found in patients with bone-only and soft tissues limited disease treated with CDK 4/6 inhibitors. Conclusions: CDK 4/6 inhibitors have similar efficacy when associated with an AI in the first-line treatment of HR+ MBC, and are superior to either F or AI monotherapy, regardless of any other patients or tumor characteristics.
Palbociclib
Fulvestrant
Aromatase inhibitor
Progression-free survival
Lapatinib
Letrozole
CDK inhibitor
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Palbociclib
Letrozole
Progression-free survival
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e12541 Background: Palbociclib in combination with an aromatase inhibitor (AI) was approved as initial endocrine therapy for patients with HR+/HER2– metastatic/advanced breast cancer (mBC) in February 2015. Evidence of real world outcomes for the combination to date has been limited by small sample size and short follow-up. This study describes patient characteristics and effectiveness of palbociclib + AI as first-line therapy in a large cohort of mBC patients in US clinical practice. Methods: Utilizing Flatiron Health’s longitudinal database, a retrospective cohort study was conducted to evaluate patients with HR+/HER2– mBC who started palbociclib + AI as first-line therapy between February 3, 2015 and August, 31, 2018. Patients were evaluated retrospectively from start of palbociclib + AI therapy on or after February 3, 2015 to November 30, 2018, death, or last visit in the database, whichever came first. Real-world progression free survival (rwPFS) was defined as months from start of palbociclib + AI therapy to death or disease progression based on clinical assessment or evidence by radiographic scan/tissue biopsy. Kaplan-Meier methods were used to estimate survival proportions in overall survival (OS) and rwPFS. Results: Of 878 who met the criteria, 66.9% were white, mean age was 65.2 years, 50.8% had visceral disease (liver and/or lung involvement), and 94% were treated in community practice. Patients were followed up to 46 months. Median rwPFS was 21.9 months (95% CI = 20.1 – 28.2). At 3 years of follow-up, OS rate was 91.9%. For additional outcomes, see Table. Conclusions: These findings from the largest cohort yet evaluated for real world effectiveness confirm the effectiveness of palbociclib + AI in routine clinical practice as a standard of care for first line treatment of HR+/HER2- mBC. [Table: see text]
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Aromatase inhibitor
Hormonal Therapy
Combination therapy
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It is known that a complete recovery in patients with generalized tumor is impossible, but the use of effective treatment regimens can significantly inhibit the development of the disease. The main goal of treatment of metastatic breast cancer is to increase overall survival, time to disease progression, improvethe quality of life, to prevent serious complications. In recent years, the standard of first−line hormone therapy in postmenopausal patients has been the use of aromatase inhibitors. Recently, a new class of drugs has emerged that can increase the effectiveness of hormone therapy, which significantly strengthens the position of this method in metastatic breast cancer. A clinical trial of PALOMA−2 and its findings are presented: the palbociclib + letrozole protocol as first−line therapy in postmenopausal patients with estrogen−positive Her2 new negative advanced breast cancer improves the objective response rate and clinical efficacy compared to letrozole monotherapy. The overall incidence of adverse responses was higher in patients treated with palbociclib + letrozole compared with placebo + letrozole. This clinical case demonstrates the possibility of long−term effective disease control in metastatic breast cancer. Literature data and personal experience show high efficacy of the combined protocol of hormone therapy and inhibitors of cyclin−dependent kinases 4/6. The use of such protocols is advisable in patients with multiple bone metastases, while achieving an effective reduction of pain. The use of such regimens is possible in patients with a low ECOG score who cannot tolerate chemotherapy with more severe toxicity. Key words: metastatic breast cancer, aromatase inhibitors, palbociclib.
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Aromatase inhibitor
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Aromatase inhibitor
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For men with metastatic breast adenocarcinoma standard therapies typically involve the same therapies used for woman. Recently the FDA approved the aromatase inhibitor letrozole combined with the inhibitor of cyclin dependent kinase 4/6 (CDK4/6) palbociclib as first line therapy for women with metastatic breast cancer.
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Abstract: Among pre- and postmenopausal women with hormone receptor-positive (HR+) breast cancer (BC), combinations of an aromatase inhibitor (AI) or fulvestrant with a CDK 4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) have demonstrated improved progression-free survival (PFS) and overall survival (OS) compared to standard single-agent hormone therapy alone as first-line therapy for de novo metastatic disease or relapse during or after adjuvant therapy and no previous therapies in an advanced setting. We here reviewed clinical data about ribociclib in advanced and early BC. Also, we shed light on patient selection and special settings in which medical oncologists urgently await an advance in treatment. Ribociclib was FDA-approved in combination with letrozole based on a Phase III study in which 668 postmenopausal women with HR+, HER2-negative recurrent or metastatic BC were treated with first-line letrozole with or without ribociclib. For patients with metastatic disease at presentation or after a course of AIs, the results of the MONALEESA-3 trial suggest ribociclib's efficacy in combination with fulvestrant, and this combination is FDA-approved for initial- and subsequent-line endocrine therapy for postmenopausal women with metastatic hormone receptor-positive, HER2-negative BC. In adjuvant and neoadjuvant settings, the use of CDK 4/6 inhibitors may be useful to boost outcomes in high-risk patients with HR+ BC, but data contrast with those of a phase III study, which produced positive results. New combinations are being explored in upfront disease (neoadjuvant) or in association with other targeted agents in metastatic disease. Compared to other CDK 4/6 available, ribociclib has a higher incidence of liver function test abnormalities than the other agents and can cause QTc prolongation, and therefore may be prudently avoided in patients with cardiac morbidities or other risk factors for QTc prolongation (drugs, interactions). In these cases, different agents (palbociclib or abemaciclib) may be used. In conclusion, ribociclib with letrozole or with fulvestrant is effective for the entire spectrum of patients with HR+ BC in the advanced setting. Ribociclib has all the characteristics of an innovative drug able to change the clinical practice and most BC patients' prognoses. Keywords: breast cancer, ribociclib, CDK 4/6 inhibitors, review
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Letrozole
Palbociclib
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Exemestane
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Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase inhibitors as the first-line standard-of-care for patients with hormone receptor-positive, HER2-negative metastatic breast cancer.
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