ribociclib and Neoplasm-Metastasis

Topics: Aminopyridines; Breast Neoplasms; Cardiac Conduction System Disease; Clinical Trials, Phase III as Topic; Female; Humans; Neoplasm Metastasis; Purines; Randomized Controlled Trials as Topic; Risk Factors

Topics: Alopecia; Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Breast Neoplasms; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Estrogen Receptor alpha; Female; Fulvestrant; Germany; Humans; Incidence; Neoplasm Metastasis; Piperazines; Protein Kinase Inhibitors; Purines; Pyridines; Quality of Life; Randomized Controlled Trials as Topic; Receptors, Progesterone; Survival Rate; Tamoxifen

Palbociclib, ribociclib and abemaciclib have all been approved in combination with endocrine therapy in hormone-receptor positive, HER2 negative metastatic breast cancer. While the efficacy of these drugs appears similar, differences in safety and tolerability are apparent.. We searched PubMed and ASCO, ESMO and SABCS proceedings to identify randomized trials of palbociclib, ribociclib and abemaciclib. Data on common and serious adverse events (AE) were extracted for each approved drug. The odds ratio for each AE and the hazard ratio for progression-free survival were calculated relative to endocrine therapy alone. A network meta-analysis was then performed for each endocrine therapy backbone (aromatase inhibitor (AI) or fulvestrant) to compare ribociclib and abemaciclib to palbociclib.. 8 trials were included in the analysis and comprised 2799 patients receiving cyclin-dependent kinase 4/6 inhibitors palbociclib: 873 patients; ribociclib: 1153 patients; abemaciclib: 773 patients. In 5 trials (1524 patients), the endocrine therapy backbone was an AI and in 3 trials (1275 patients) it was fulvestrant. Compared to palbociclib, ribociclib and abemaciclib showed significantly lower grade 3-4 neutropenia, but significantly higher GI toxicity. Treatment discontinuation was higher with abemaciclib than other drugs. Efficacy of the 3 drugs was similar. Compared to palbociclib, for AI backbone, the HR for PFS for ribociclib was 0.98 and for abemaciclib 1.02. For fulvestrant backbone, the HR were 0.88 and 0.93 respectively.. Palbociclib, ribociclib and abemaciclib have comparable efficacy, but differences in safety and tolerability. Abemaciclib has worse tolerability with significantly higher treatment discontinuation likely due to GI toxicity.

Topics: Aminopyridines; Antineoplastic Agents; Benzimidazoles; Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Female; Humans; Neoplasm Metastasis; Network Meta-Analysis; Piperazines; Protein Kinase Inhibitors; Purines; Pyridines; Randomized Controlled Trials as Topic

To review the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of ribociclib (LEE011, Kisqali) in hormone receptor-positive/human epidermal growth factor receptor-2-negative (HR+/HER2-) metastatic breast cancer.. A PubMed search was performed using the terms 'Ribociclib', 'Kisqali', and 'LEE011' between May 2018 and November 2018. References of published articles and reviews were also assessed for additional information.. English-language preclinical and clinical studies on the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of ribociclib were evaluated.. Ribociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, is Food and Drug Administration (FDA) approved in combination with endocrine therapy for treatment of HR+/HER2- advanced or metastatic breast cancer in premenopausal/perimenopausal and postmenopausal women. Three phase III trials have evaluated ribociclib in combination with endocrine therapy, including letrozole, anastrozole, tamoxifen, and fulvestrant. These studies found that ribociclib 600 mg/d, 21 days on, 7 days off, leads to a significantly greater median progression-free survival (PFS), ranging from 8 to 13 months. Ribociclib is well tolerated in elderly patients, maintains health-related quality of life, and significantly reduces pain scores. The dose-limiting toxicities found in phase I studies were neutropenia, thrombocytopenia, and QTc prolongation. Common adverse effects seen in phase III trials include neutropenia, leukopenia, nausea, diarrhea, vomiting, and fatigue. Relevance to Patient Care and Clinical Practice: Literature on the safety and efficacy of ribociclib as well as its place in therapy in comparison to other FDA-approved CDK4/6 inhibitors for breast cancer is discussed.. Ribociclib, when added to endocrine therapy, significantly improves PFS and has manageable toxicity in premenopausal/perimenopausal and postmenopausal women with HR+/HER2- advanced breast cancer.

Topics: Adult; Aged; Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease Progression; Female; Humans; Neoplasm Metastasis; Premenopause; Purines; Quality of Life; Receptor, ErbB-2; Receptors, Estrogen

The emergence of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors marked a significant advancement in the treatment of advanced breast cancer. Ribociclib is an orally bioavailable, highly selective inhibitor of CDK4/6. In combination with various endocrine therapies, ribociclib has demonstrated clinical activity as a first-line therapy for patients with HR+, HER2- advanced breast cancer, without compromising the favorable toxicity profile associated with endocrine therapy. Thus, ribociclib is now considered a new standard of care for HR+, HER2- advanced breast cancer. Areas covered: This review provides a concise overview of the preclinical and clinical development of ribociclib, including evidence of its clinical activity and safety profile when combined with endocrine therapy in HR+, HER2- advanced breast cancer. Expert commentary: CDK4/6 inhibition represents a promising treatment option for patients with HR+ metastatic breast cancer. Ribociclib significantly improved progression-free survival in patients receiving first-line endocrine therapy for HR+, HER2- advanced breast cancer. Planned and ongoing trials investigating ribociclib in combination with other endocrine therapies and in various clinical settings will help to determine the optimal treatment sequence for different patient populations.

Topics: Aminopyridines; Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Drug Design; Female; Humans; Neoplasm Metastasis; Progression-Free Survival; Purines

Cyclin D-cyclin-dependent kinase (CDK) 4/6-inhibitor of CDK4/6-retinoblastoma (Rb) pathway hyperactivation is associated with hormone receptor-positive (HR+) breast cancer (BC). Ribociclib is an orally bioavailable, highly selective small molecule inhibitor of CDK4/6 that induces G1 arrest at sub-micromolar concentrations in a variety of pRb-positive cancer cells in vitro. Ribociclib is a new standard of care for metastatic HR+/HER2 negative metastatic breast cancer. Area covered: In this article, we review the preclinical and clinical development of ribociclib as well as discussing the role for novel applications of these agents outside the arena of HR-positive, HER2-negative advanced breast cancer. Expert opinion: Results of pivotal phase II and III trials investigating ribociclib in patients with advanced-stage (HR)-positive breast cancer have demonstrated a substantial improvement in progression-free survival, with a safe toxicity profile. Mechanisms of acquired resistance to CDK4/6 inhibitors are beginning to emerge and might enable rational post-CDK4/6 inhibitor therapeutic strategies to be identified. Extending the use of CDK4/6 inhibitors beyond ER-positive breast cancer is challenging, and will likely require biomarkers that are predictive of a response. The use of combination therapies to optimize CDK4/6 targeting is under development.

Topics: Aminopyridines; Antineoplastic Agents; Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Humans; Neoplasm Metastasis; Purines; Receptor, ErbB-2

The cyclin D-cyclin dependent kinase (CDK) 4/6-inhibitor of CDK4 (INK4)-retinoblastoma (Rb) pathway plays a crucial role in cell cycle progression and its dysregulation is an important contributor to endocrine therapy resistance. CDK4/6 inhibitors trigger cell cycle arrest in Rb protein (pRb)-competent cells. Recent years have seen the development of selective CDK4/6 inhibitors, which have delivered promising results of efficacy and manageable safety profiles. The main objective of this review is to discuss preclinical and clinical data to date, and ongoing clinical trials with palbociclib, ribociclib, and abemaciclib in breast cancer.. A literature search of above topics was carried out using PubMed and data reported at international oncology meetings and clinicaltrials.gov were included.. The highly selective oral CDK4/6 inhibitors have been tested in combination with endocrine therapy in Phase III studies in metastatic breast cancer. Results led to the US Food and Drug Administration approval of palbociclib (PD0332991) and ribociclib (LEE011), and abemaciclib (LY2835219) is in development. Studies of these agents, in combination with endocrine therapy, are also underway in ER-positive early breast cancer in the neoadjuvant and adjuvant settings. Moreover, they are also being investigated with other agents in the advanced setting and in triple negative breast cancer.. After having demonstrated impressive activity in ER-positive, HER2-negative metastatic breast cancer, currently CDK4/6 inhibitors are in further development. It is obvious that this class of agents with their efficacy, low and easily manageable toxicity, and oral dosage is a very important treatment option for breast cancer patients.

Topics: Aminopyridines; Antineoplastic Agents; Benzimidazoles; Biomarkers, Tumor; Breast Neoplasms; Clinical Trials as Topic; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Female; Humans; Molecular Targeted Therapy; Neoplasm Metastasis; Neoplasm Staging; Piperazines; Protein Kinase Inhibitors; Purines; Pyridines; Randomized Controlled Trials as Topic; Treatment Outcome

CDK4/6 inhibitors are a promising new class of drugs for hormone-receptor-positive breast cancer and have been shown to overcome and delay hormone resistance in advanced breast cancer. Ribociclib, a selective oral inhibitor of CDK4/6, was approved by the US FDA for first-line treatment of hormone-receptor-positive/HER2-negative metastatic breast cancer. This review summarizes the clinical evidence available for ribociclib, from preclinical data to the pivotal studies, with a special focus on toxicity and its management. In addition, this article reviews potential new combinations under study, as well as ongoing clinical trials both in the metastatic and early setting. Finally, this review compares ribociclib activity and toxicity with those of the drugs of the same class (palbociclib and abemaciclib).

Topics: Aminopyridines; Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Clinical Trials as Topic; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Drug Evaluation, Preclinical; Female; Humans; Molecular Targeted Therapy; Neoplasm Metastasis; Neoplasm Staging; Protein Kinase Inhibitors; Purines; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone

The introduction of CDK4/6 inhibitors, such as ribociclib, has changed the treatment landscape for post-menopausal women with HR+/HER2- advanced or metastatic breast cancer. As first-line treatment of HR+/HER2- MBC, the addition of a CDK4/6 inhibitor to an aromatase inhibitor improves progression-free survival compared to an aromatase inhibitor alone. Areas covered: In this drug profile, we review the current market for HR+/HER2- MBC, as well as the characteristics, mechanism, pharmacology, pharmacodynamics, pharmacokinetics, metabolism, clinical efficacy, toxicities, monitoring, and dosing modification of the CDK4/6 inhibitor ribociclib. Expert commentary: CDK4/6 inhibitors, such as ribociclib, improve outcomes in post-menopausal women with HR+/HER2- MBC. The most common toxicity of ribociclib is neutropenia, which is generally not complicated and can be managed with dose modification and/or supportive care measures. Additional research will help better define the optimal clinical use of ribociclib.

Topics: Aminopyridines; Antineoplastic Agents; Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Disease-Free Survival; Dose-Response Relationship, Drug; Female; Humans; Neoplasm Metastasis; Neutropenia; Postmenopause; Purines; Receptor, ErbB-2

The population pharmacokinetics (popPK) of ribociclib and population pharmacokinetic/pharmacodynamic (PK/PD) relationship between ribociclib and absolute neutrophil count (ANC) were characterized in patients with cancer. PopPK and ANC PK/PD modeling were both conducted in 2 rounds per data availability. Initial models were developed based on data sets from early-phase trials and qualified using external data from the phase III MONALEESA-2 trial. The second round of analyses was performed using updated data sets that included 2 more phase III trials (MONALEESA-3 and -7). The popPK and ANC PK/PD models adequately described the data and demonstrated reasonable predictive ability. Covariate analysis showed that ribociclib PK were not affected by age, sex, race, baseline Eastern Cooperative Oncology Group (ECOG) status (grade 1), mild/moderate renal impairment, mild hepatic impairment, or concomitant use of combination partners, including aromatase inhibitors (letrozole, anastrozole) or fulvestrant, proton-pump inhibitors, or weak cytochrome P450 3A4/5 inhibitors. Body weight had no impact on ribociclib clearance to warrant dose adjustment. The ANC PK/PD relationship was not affected by age, weight, sex, race, baseline ECOG status (grade 1), or concomitant use of letrozole, anastrozole, or fulvestrant. The PK/PD analysis confirmed reversibility of ribociclib's effect on ANC; it also suggested that lowering the dose of ribociclib would mitigate ANC decrease and neutropenia risk. The popPK and ANC PK/PD analyses support the use of ribociclib in combination with an aromatase inhibitor or fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced or metastatic breast cancer without dose adjustment in subpopulations, and the use of dose interruption/reduction to mitigate potential treatment-emergent neutropenia.

Topics: Adult; Age Factors; Aged; Aminopyridines; Antineoplastic Agents; Area Under Curve; Body Weight; Breast Neoplasms; Drug Interactions; Female; Humans; Kidney Function Tests; Liver Function Tests; Male; Metabolic Clearance Rate; Metabolic Networks and Pathways; Middle Aged; Models, Biological; Neoplasm Metastasis; Neutrophils; Purines; Racial Groups; Receptor, ErbB-2; Receptors, Progesterone; Sex Factors

Breast cancer is the most common female tumour type and accounts for the leading cancer mortality in women worldwide. Up to 75% of breast cancers express the oestrogen receptor or progesterone receptor (hormone-receptor-positive). Aromatase inhibitors were the preferred first-line treatment option. New and acquired resistance to hormonal blockade has led to the development of targeted treatments. Cyclin-dependent kinases (CDKs) are a large family of serine-threonine kinases that play an important role in regulating cell cycle progression: palbociclib, ribociclib, and abemaciclib. We conducted a study to evaluate the efficacy of CDK inhibitors (CDKi) plus aromatase inhibitor in hormone-receptor-positive/HER2-negative ABC patients with visceral disease, postponing the use of chemotherapeutic agents and strengthening the power of endocrine agents. We enrolled 22 patients treated with CDKi (palbocilib) plus aromatase inhibitor (group A) and 38 patients treated with chemotherapy (group B). Our small study confirms the effectiveness of treatment with CDKi plus aromatase inhibitor, even in patients with visceral metastases, when compared with chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Follow-Up Studies; Humans; Letrozole; Middle Aged; Neoplasm Metastasis; Piperazines; Prognosis; Purines; Pyridines; Receptor, ErbB-2; Retrospective Studies; Survival Rate; Viscera

CDK 4/6 inhibitors have given patients with estrogen receptor (ER)-positive/HER2-negative (ER+/HER2ࢤ) advanced metastatic breast cancer important new therapeutic options. Abemaciclib is different to the other two licensed and approved CDK 4/6 inhibitors, palbociclib and ribociclib, both in dosing schedule (continuous vs intermittent) and toxicity profile (less neutropenia, more diarrhea), yet the magnitude of clinical benefit seen in first- and second-line studies is very similar. One of the key issues for clinicians is when to use these therapies. Ultimately, the biggest impact of abemaciclib could be in the adjuvant setting if the current MONARCH-E trial in high-risk node-positive patients is positive. The emerging biomarker work in the early breast cancer setting (i.e., neoMONARCH) may determine which tumors are most sensitive to abemaciclib.

Topics: Aminopyridines; Animals; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Drug Evaluation; Female; Follow-Up Studies; Humans; Mice; Molecular Targeted Therapy; Neoplasm Metastasis; Piperazines; Prognosis; Purines; Pyridines; Receptors, Estrogen; Survival Rate; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

The phase 3 MONALEESA-2 study demonstrated that addition of ribociclib (RIB) to letrozole (LET) significantly improved progression-free survival (PFS) in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC). Here, we evaluated duration of response (DoR), tumor shrinkage, PFS by treatment-free interval (TFI), and health-related quality of life (HRQoL).. Postmenopausal women (N = 668) with HR+ , HER2- ABC and no prior systemic therapy for ABC were randomized to RIB (600 mg/day; 3 weeks on/1 week off) plus LET (2.5 mg/day; continuous) or placebo (PBO) plus LET. Primary end point was PFS; HRQoL was the secondary end point; DoR was exploratory end point and PFS by TFI was post hoc analysis.. Of 501 pts with measurable disease and confirmed complete or partial response, median DoR was 26.7 months (95% CI, 24.0-NR) in the RIB arm versus 18.6 months (95% CI, 14.8-23.1) in the PBO arm. At 8 weeks, more pts in the RIB arm (32%) versus the PBO arm (17%) experienced best percentage change ≥ 60%. The average pain reduction was greater in the RIB arm (26%) versus the PBO arm (15%). PFS benefit was seen with RIB vs PBO, irrespective of TFI.. RIB plus LET versus PBO plus LET is associated with earlier and more durable tumor response, greater degree of tumor shrinkage and pain reduction, and PFS benefit irrespective of TFI. These data further support RIB plus LET as a first-line treatment option for postmenopausal women with HR+ , HER2- ABC.

Topics: Adult; Aged; Aged, 80 and over; Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Female; Humans; Kaplan-Meier Estimate; Letrozole; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Purines; Quality of Life; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Treatment Outcome; Young Adult

There is scant data from India on efficacy and safety of palbociclib and ribociclib in routine clinical practice.. This retrospective, observational, single institution study included patients with estrogen and/or progesterone receptor positive and human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancers, who received palbociclib or ribociclib with any partner endocrine therapy in any line of treatment between January 2016 and June 2019. Data were analyzed for progression-free survival (PFS), overall survival (OS) and toxicity.. The study included 101 female patients with median age of 57 (IQR 48-62) years, of whom 80 (79.2%) were postmenopausal, 79 (78.2%) received palbociclib or ribociclib in second- or later-line treatment, 59 (58.4%) received fulvestrant and 41 (40.6%) received an aromatase inhibitor. In first-line treatment, at a median follow-up of 21.7 (0.5-41.9) months, median PFS and OS were 21.1 (95%CI 16.36-not estimable) months and not reached, respectively. In second- or later-line setting, at a median follow-up of 17.2 (0.5-43.7) months, median PFS and OS were 5.98 (95%CI 4.96-7.89) months and 20.2 (95%CI 14.1-not estimable) months, respectively. Grade 3-4 neutropenia and febrile neutropenia were seen in 45 (45.0%) and 9 (9.0%) patients, respectively while dose reduction was required in 32 (31.7%) patients. In multivariable Cox regression analysis, first-line setting (HR 0.49, 95%CI 0.25-0.97, p = 0.043) and ECOG performance status 1 (HR 0.43, 95%CI 0.20-0.91, p = 0.028) were significantly associated with PFS while only ECOG PS 1 was significantly associated (HR 0.04, 95%CI 0.008-0.206, p = 0.000) with OS.. Palbociclib and ribociclib, when used in routine clinical practice in first or subsequent lines of treatment, resulted in efficacy and toxicity outcomes in concordance with those expected from pivotal trials.

Topics: Aged; Aminopyridines; Breast Neoplasms; Databases, Factual; Disease-Free Survival; Female; Follow-Up Studies; Humans; Middle Aged; Neoplasm Metastasis; Piperazines; Purines; Pyridines; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; Survival Rate

The ongoing, Phase Ib MONALEESASIA study is evaluating the efficacy and safety of ribociclib plus endocrine therapy in Asian patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Eligible patients from Japan, Hong Kong, and Singapore were enrolled in this 2-phase study consisting of a dose-escalation phase to determine the maximum-tolerated dose and the recommended Phase II dose of ribociclib plus letrozole, and a dose-expansion phase to evaluate safety and tolerability of ribociclib plus letrozole, fulvestrant, or tamoxifen. An exploratory biomarker analysis evaluating expression of target genes was also conducted. In the dose-escalation phase, the maximum-tolerated/recommended Phase II doses of ribociclib were lower in Japanese patients (300 mg) than in Asian non-Japanese patients (600 mg). Ribociclib plus endocrine therapy at the recommended Phase II dose had a manageable safety profile, with neutropenia and elevated liver transaminases being the most common adverse events leading to dose modifications or discontinuations, and it demonstrated evidence of clinical activity in both Japanese and Asian non-Japanese patients. Preliminary efficacy in Asian populations is similar to that observed in White populations studied in previous ribociclib (MONALEESA) trials. Biomarker analysis demonstrated suppression of pharmacodynamic biomarker gene expression, indicating inhibition of target genes by ribociclib combined with endocrine therapy. Results from the ongoing study support the use of ribociclib in combination with letrozole in Asian non-Japanese patients at the same dose (600 mg) as White patients. In Japanese patients, a lower dose of ribociclib (300 mg) should be considered. Clinicaltrials.gov: NCT02333370.

Topics: Aged; Aged, 80 and over; Aminopyridines; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Asian People; Biomarkers; Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Female; Humans; Japan; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Protein Kinase Inhibitors; Purines; Treatment Outcome

Cyclin dependent kinases 4/6 (CDK4/6) inhibitors gained an essential role in the treatment of metastatic breast cancer. Nevertheless, data regarding their use in combination with radiotherapy are still scarce. We performed a retrospective preliminary analysis of breast cancer patients treated at our Center with palliative radiation therapy and concurrent CDK4/6 inhibitors. Toxicities were measured according to CTCAE 4.0, local response according to RECIST 1.1 or PERCIST 1.0 and pain control using verbal numeric scale. 18 patients (32 treated sites) were identified; 50% received palbociclib, 33.3% ribociclib and 16.7% abemacliclib. Acute non-hematologic toxicity was fair, with the only exception of a patient who developed G3 ileitis. During 3 months following RT, 61.1% of patients developed G 3-4 neutropenia; nevertheless no patient required permanent suspension of treatment. Pain control was complete in 88.2% of patients three months after radiotherapy; 94.4% of patients achieved and maintained local control of disease. Radiotherapy concomitant to CDK4/6 inhibitors is feasible and characterized by a fair toxicity profile, with isolated episodes of high-grade reversible intestinal toxicity. Rate of G 3-4 neutropenia was comparable with that measured for CDK4/6 inhibitors alone. Promising results were reported in terms of pain relief and local control of disease.

Topics: Aminopyridines; Breast Neoplasms; Combined Modality Therapy; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Female; Humans; Ileitis; Molecular Targeted Therapy; Neoplasm Metastasis; Neutropenia; Outcome Assessment, Health Care; Piperazines; Protein Kinase Inhibitors; Purines; Pyridines; Radiotherapy; Retrospective Studies

Combination ribociclib and aromatase inhibitors are currently the preferred treatment in Australia for newly diagnosed hormone receptor positive metastatic breast cancer in the absence of visceral crisis. In our case series of 32 patients, 28% experienced grade 1 elevations in creatinine, a toxicity that was under-recognised in large phase III studies. Creatinine rise appears to be due to a reversible inhibition of renal efflux transporters rather than an acute kidney injury in the majority of cases.

Topics: Aged; Aminopyridines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Creatinine; Disease-Free Survival; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; New South Wales; Purines; Receptor, ErbB-2; Retrospective Studies

On March 13, 2017, the FDA approved ribociclib (KISQALI; Novartis Pharmaceuticals Corp.), a cyclin-dependent kinase 4/6 inhibitor, in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer. The approval was based on a randomized, double-blind, placebo-controlled, international clinical trial (MONALEESA-2). A total of 668 patients were randomized to receive either ribociclib plus letrozole (

Topics: Aminopyridines; Antineoplastic Agents; Breast Neoplasms; Clinical Trials as Topic; Drug Approval; Female; Humans; Neoplasm Metastasis; Neoplasm Staging; Postmenopause; Protein Kinase Inhibitors; Purines; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Research Design; Treatment Outcome

Topics: Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Benzimidazoles; Breast Neoplasms; Carcinoma, Lobular; Colonic Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Female; Humans; Letrozole; Middle Aged; Neoplasm Metastasis; Piperazines; Protein Kinase Inhibitors; Purines; Pyridines; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone

Topics: Aminopyridines; Antineoplastic Agents; Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Female; Humans; Neoplasm Metastasis; Protein Kinase Inhibitors; Purines; Signal Transduction; Treatment Outcome