Use Of Cyclin-dependent Kinase Research Articles

Single institution retrospective review of patients with metastatic hormone receptor positive breast cancer receiving first line therapy of CDK4/6 inhibitors.

e13090 Background: Breast cancer continues to be the most commonly diagnosed cancer in women. The majority of these cancers are estrogen positive (ER+) and about 6% of new cases are stage 4 at time of diagnosis. The current standard of care for postmenopausal women with stage 4 ER+ breast cancer is a combination of an aromatase inhibitor (AI) with a cyclin-dependent kinase (CDK) 4/6 inhibitor. Based on Medicare data claim analysis from IQVIA, CDK 4/6 inhibitors are being used nationally in the first line setting in 56% of cases where 24% of cases were treated with AI monotherapy. The state of Kentucky currently lies below this national average by using this treatment regimen in 38% of cases where 47% of cases are treated with AI monotherapy. The reason for this discrepancy between the national average and Kentucky is currently unknown. To further understanding, we have conducted an internal review of adherence to the guidelines. Methods: This is a single center retrospective study done at University of Louisville, Brown Cancer Center. Data was collected on patients who had biopsy proven metastatic hormone positive breast cancer from July 2021 until May 2023 (n=41). Collected characteristics include age on diagnosis, tumor grade, sites of metastatic disease, first line treatment received, choice of CDK4/6 inhibitor if received, and prior exposure to chemotherapy or anti-estrogen therapy. Results: In our cohort of 41 patients, we found that 63.4% (n=26) of patients received an AI and CDK4/6 inhibitor in the first line. There were 4.88% (n=2) of patients who received AI monotherapy, 21.9% (n=9) received Fulvestrant and CDK4/6 inhibitor, 4.88 % (n=2) received AI and Fulvestrant and 4.88% (n=2) received Fulvestrant alone. In total, patients who received estrogen therapy plus CDK4/6 inhibitor totaled 85% of new patients (n=35). Conclusions: This internal review showed our institution to be compliant with endocrine therapy and CDK 4/6 inhibitor in front-line treatment for the majority of metastatic ER+ patients. Given the supportive data for use of CDK 4/6 inhibitors in front-line treatment, the compliance is expected to be much higher. We recommend continued discussion amongst oncology providers to help identify barriers to treatment and determine the causes for poor compliance in the state of Kentucky.

The Use of Cyclin-Dependent Kinase 4/6 Inhibitors in Elderly Breast Cancer Patients: What Do We Know?

Breast cancer (BC) incidence increases with age, particularly in HR-positive/HER2-negative subtypes. Cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6is) alongside endocrine therapy (ET) have emerged as promising treatments for HR-positive/HER2-negative advanced and early BC. However, their efficacy, safety, and impact on quality of life (QoL) in older and frail patients remain underexplored. This position paper assesses the existing literature from 2015 to 2024, focusing on CDK4/6is use in patients aged 65 years and older with HR-positive/HER2-negative BC. Our analysis methodically addresses critical questions regarding the utilization of CDK4/6is in the elderly BC patient population, organizing findings from the metastatic and adjuvant settings. In the metastatic setting, CDK4/6is significantly improve progression-free survival (PFS), paralleling benefits observed in younger patients, and suggest potential overall survival (OS) benefits, warranting further investigation. Despite an increased incidence of grade ≥ 3 adverse events (AEs), such as neutropenia and asthenia, CDK4/6is present a markedly lower toxicity profile compared to traditional chemotherapy, with manageable side effects. QoL analysis indicates that integrating CDK4/6is into treatment regimens does not significantly impact elderly BC patients' daily life and symptom management. Special attention is given to frail subgroups, and personalized approaches are recommended to balance efficacy and adverse effects, such as starting with ET alone and introducing CDK4/6is upon progression in patients with a low disease burden. Transitioning to the adjuvant setting, early results, particularly with abemaciclib, indicate positive effects on disease-free survival (DFS), emphasizing the need for continued analysis to validate these findings and assess long-term implications. However, data on older patients are insufficient to conclude whether they truly benefit from this treatment. Overall, CDK4/6is present a favorable benefit-risk profile in older BC patients, at least in advanced BC; however, further research is warranted to optimize treatment strategies and improve outcomes in this population.

Ribociclib-induced visual hallucination in a patient with metastatic breast cancer.

Cyclin-dependent kinase (CDK) 4/6 inhibitors are widely used in combination with aromatase inhibitors or fulvestrant for the treatment of locally advanced or metastatic hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) breast cancer. Hematological toxicities (e.g. neutropenia, thrombocytopenia, anemia, lymphopenia, or febrile neutropenia), infections, decreased appetite, exhaustion, headache, dizziness, cough, nausea, vomiting, diarrhea, alopecia, rash, increased alanine aminotransferase and aspartate aminotransferase levels, and QT interval prolongation are frequent side effects associated with the use of CDK 4/6 inhibitors. However, to our knowledge, no case of hallucination associated with CDK 4/6 inhibitor use has been described in the English-language literature. We report a case of a 72-year-old woman with metastatic breast cancer who developed visual hallucinations after receiving ribociclib, a CDK 4/6 inhibitor, and letrozole for 3 days. Cranial imaging and blood tests did not reveal the cause of the hallucinations. The visual hallucinations completely resolved within 4 days after the ribociclib treatment was terminated. The patient received only letrozole for 2 weeks, and ribociclib treatment was restarted 2 weeks later. Visual hallucinations recurred on the third day of treatment, and ribociclib treatment was discontinued again. The patient recovered completely from visual hallucinations 4 days after discontinuation. Subsequently, treatment was continued with letrozole and palbociclib, another CDK 4/6 inhibitor. Hallucinations did not recur during follow-up. To our knowledge, this is the first reported case of hallucinations caused by ribociclib; notably, it shows that symptoms may develop in the early stage of treatment.

Health-related quality of life of women with breast cancer being treated with hormone therapy: A scoping review.

To map the evidence available in the literature on the health-related quality of life of women with breast cancer using hormone therapy. This review followed the Joanna Briggs Institute methodological recommendations and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews reporting guidelines. Searches were performed in nine databases using descriptors, synonyms and keywords; grey literature was also included. The review protocol was registered with the Open Science Framework under doi: http://doi.org/10.17605/OSF.IO/347FM. Inclusion criteria were established according to the Population, Concept, and Context strategy. The selection of studies was performed by two independent reviewers with the aid of RAYYAN software and disagreements were resolved by a third reviewer. The main information from the included articles was grouped into textual categories and presented by means of a narrative synthesis. A total of 5419 records were identified, of which 42 studies fully met the eligibility criteria. Most were multicenter studies (42.9%) and randomized controlled trials (62%). Most studies addressed anastrozole (39.5%), letrozole (34.2%), and tamoxifen (26.3%), which were studied alone or in combination. The most widely used health-related quality-of-life assessment tool was the EORTC-QLQ-C30. The concomitant use of hormone therapy and cyclin-dependent kinase inhibitors 4 and 6 showed improvement in health-related quality of life. In recent years there has been an increase in studies focused on health-related quality of life, and the evidence pointed to relevant information on health-related quality of life and the use of endocrine therapy, tamoxifen in combination with aromatase inhibitors, as well as aromatase inhibitor alone and the use of cyclin-dependent kinase 4 and 6.

Regulatory Approval, Reimbursement, and Clinical Use of Cyclin-Dependent Kinase 4/6 Inhibitors in Metastatic Breast Cancer in the Netherlands

This study found that CDK4/6 inhibitors rapidly reached many eligible patients with metastatic breast cancer and were adopted gradually over time in the Netherlands. Adoption of innovative medicines may be further optimized, and better transparency of the availability of new medicines during different phases of the postapproval access pathway is needed. This cohort study reviewed approval and reimbursement decisions of the CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib and estimated the number of patients with metastatic breast cancer who were eligible for these medicines compared with the actual use in clinical practice. The study used nationwide claims data that were obtained from the Dutch Hospital Data. Claims and early access data for patients with hormone receptor-positive and ERBB2 (formerly HER2)-negative metastatic breast cancer who were treated with CDK4/6 inhibitors from November 1, 2016, to December 31, 2021, were included. The number of new cancer medicines that are being approved by regulatory agents is increasing exponentially. Yet little is known about the pace at which these medicines reach eligible patients in daily clinical practice during different phases of the postapproval access pathway. Description of the postapproval access pathway, monthly number of patients who were treated with CDK4/6 inhibitors in clinical practice, and estimated number of patients who were eligible for treatment. Aggregated claims data were used, and patient characteristics and outcomes data were not collected. To describe the entire postapproval access pathway of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in the Netherlands, from regulatory approval to reimbursement and to investigate the adoption of these medicines in clinical practice among patients with metastatic breast cancer. Three CDK4/6 inhibitors have received European Union-wide regulatory approval for the treatment of HR-positive and ERBB2-negative metastatic breast cancer since November 2016. In the Netherlands, the number of patients who have been treated with these medicines increased to approximately 1847 (based on 1 624 665 claims over the entire study period) from approval to the end of 2021. Reimbursement for these medicines was granted between 9 and 11 months after approval. While awaiting reimbursement decisions, 492 patients received palbociclib, the first approved medicine of this class, via an expanded access program. By the end of the study period, 1616 patients (87%) were treated with palbociclib, whereas 157 patients (7%) received ribociclib, and 74 patients (4%) received abemaciclib. The CKD4/6 inhibitor was combined with an aromatase inhibitor in 708 patients (38%) and with fulvestrant in 1139 patients (62%). The pattern of use over time appeared to be somewhat lower compared with the estimated number of eligible patients (1847 vs 1915 in December 2021), especially in the first 2.5 years after approval.

Vitiligo-like lesions associated with ribociclib in a woman with metastatic breast cancer.

Cyclin-dependent kinase 4/6 inhibitors are new generation drugs that have recently been used in patients with hormone receptor-positive and human epidermal growth factor receptor 2-negativenegative metastatic breast cancer. Recent studies have shown that the use of cyclin-dependent kinase 4/6 inhibitors significantly improves the outcomes of these patients. The most common side effects of cyclin-dependent kinase 4/6 inhibitors are hematological toxicity, gastrointestinal side effects, and fatigue. We aimed to present a case of metastatic breast cancer who was treated with ribociclib and developed vitiligo-like lesions after treatment. A 56-year-old female patient was diagnosed with locally advanced hormone receptor (+)/human epidermal growth factor receptor 2 (-) breast cancer in May 2000. She was followed up with hormonal therapy after adjuvant chemotherapy and radiotherapy. The patient progressed with lung metastases in 2012. Ribociclib, anastrozole, and leuprolide acetate were started in November 2021 after multiple-line chemotherapy. After six cycles of ribociclib, vitiligo-like lesions that developed in the last 1 month were detected on the upper extremities, both hands, neck, chest, and upper back. The patient was referred to dermatology. Topical immunosuppressive therapy and oral corticosteroids were recommended. At the first and third-month follow-up examinations, vitiligo-like lesions were observed to persist. Vitiligo-like lesions are not a life-threatening side effect. However, it significantly affects the quality of life and disrupts the patient's compliance with treatment. Cyclin-dependent kinase 4/6 inhibitors can inhibit cell division or cause premature cell death by acting on the melanocyte cell cycle.

Genomic Aberrations in Circulating Tumor DNAs from Palbociclib-Treated Metastatic Breast Cancer Patients Reveal a Novel Resistance Mechanism.

Simple SummaryThe combination of CDK4/6 inhibitors and endocrine therapy is now considered the standard of care for patients with estrogen receptor-positive (ER+) breast cancer. The emerging tide of CDK4/6 inhibitor resistance urges more research to explore underlying resistance mechanisms. This study profiled circulating cell-free DNA obtained before and after palbociclib treatment in ER+ metastatic breast cancer patients using 91-gene panel sequencing. The results revealed that the acquisition of CCNE1 mutations and the loss of TSC2 mutations confer an unfavorable prognosis, suggesting that these mutations may potentially serve as novel genomic biomarkers for treatment resistance. Future large-scale population studies and mechanism-focused research are needed to confirm the findings of this study and elucidate the underlying molecular mechanisms. Ultimately, such efforts may lead to the development of improved methods to predict treatment efficacy and clinical outcomes, as well as more effective targeted treatment approaches for the benefit of breast cancer patients.Previously undescribed molecular mechanisms of resistance will emerge with the increased use of cyclin-dependent kinase 4/6 inhibitors in clinical settings. To identify genomic aberrations in circulating tumor DNA associated with treatment resistance in palbociclib-treated metastatic breast cancer (MBC) patients, we collected 35 pre- and post-treatment blood samples from 16 patients with estrogen receptor-positive (ER+) MBC, including 9 with inflammatory breast cancer (IBC). Circulating cell-free DNAs (cfDNAs) were isolated for sequencing using a targeted panel of 91 genes. Our data showed that FBXW7 and CDK6 were more frequently altered in IBC than in non-IBC, whereas conversely, PIK3CA was more frequently altered in non-IBC than in IBC. The cfDNA samples collected at follow-up harbored more mutations than baseline samples. By analyzing paired samples, we observed a higher percentage of patients with mutations in RB1, CCNE1, FBXW7, EZH2, and ARID1A, but a lower proportion of patients with mutated TSC2 at the post-treatment stage when they developed progression. Moreover, acquisition of CCNE1 mutations or loss of TSC2 mutations after treatment initiation conferred an unfavorable prognosis. These data provide insights into the relevance of novel genomic alterations in cfDNA to palbociclib resistance in MBC patients. Future large-scale prospective studies are warranted to confirm our findings.

PostMONARCH: A phase 3 study of abemaciclib plus fulvestrant versus placebo plus fulvestrant in patients with HR+, HER2-, metastatic breast cancer following progression on a CDK4 & 6 inhibitor and endocrine therapy.

TPS1117 Background: The use of cyclin dependent kinase 4 and 6 (CDK4 & 6) inhibitors plus endocrine therapy (ET) has transformed the management of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). However, most patients will experience disease progression. Identification of treatment options following progression is an unmet medical need. Additionally, as CDK4 & 6 inhibitors are now being deployed in the adjuvant setting, determination of optimal therapy following metastatic relapse is an important question. In patients with disease progression following a CDK4 & 6 inhibitor-based regimen, continuing CDK4 & 6 inhibition with abemaciclib while switching the ET backbone may provide benefit and delay the need for cytotoxic chemotherapy. Abemaciclib is an oral, selective, and potent CDK4 & 6 inhibitor administered continuously and approved as monotherapy or with ET for treatment of HR+, HER2- ABC. Abemaciclib has also been approved with ET for the adjuvant treatment of HR+, HER2-, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score ≥20%. Fulvestrant is a selective ER degrader (SERD) approved for treatment of HR+, HER2- ABC. The postMONARCH study investigates whether abemaciclib plus fulvestrant will improve outcomes in patients with HR+, HER2- ABC after disease relapse or progression after adjuvant or first-line treatment with a CDK4 & 6 inhibitor plus ET. Methods: postMONARCH is a Phase 3, global, multicenter, randomized, double-blind, placebo-controlled study in patients with HR+, HER2- ABC and with disease progression on treatment with a prior CDK4 & 6 inhibitor plus an aromatase inhibitor as initial therapy for ABC or recurrence on/after treatment with a CDK4 & 6 inhibitor plus ET in the adjuvant setting. Eligible patients are randomized 1:1 to receive abemaciclib 150 mg twice daily or placebo, plus fulvestrant. Stratification factors include geography, presence of visceral metastasis, and duration of prior CDK4 & 6 inhibitor-based regimen. The study is powered at 80% with a cumulative Type I error of 0.025 to detect the superiority of abemaciclib plus fulvestrant versus placebo plus fulvestrant in terms of investigator-assessed progression free survival. Key secondary endpoints include overall survival, PFS by blinded independent central review, objective response rate, safety, patient-reported outcomes, and pharmacokinetics. This study opened in Jan 2022, plans for approximately 122 centers in 18 countries, and anticipates enrolling ̃350 patients. Clinical trial information: NCT05169567.

Impact of the COVID-19 Pandemic on Breast Cancer Management in Portugal: A Cross-Sectional Survey-Based Study of Medical Oncologists.

IntroductionCancer care providers have faced many challenges in delivering safe care for patients during the COVID-19 pandemic. This cross-sectional survey-based study investigated the impact of the pandemic on clinical practices of Portuguese medical oncologists caring for patients with breast cancer.MethodsAn anonymous online survey comprising 42 questions gathered information regarding COVID-19 testing, treatment in (neo)adjuvant and metastatic settings, and other aspects of breast cancer management. Practices before and during the pandemic were compared, and potential differences in outcomes according to respondents’ regions, case volumes, and practice type were explored.ResultsOf 129 respondents, 108 worked in the public health system, giving a representative national picture of the impact of the COVID-19 pandemic on breast cancer management. Seventy-one percent of respondents reported a reduction in visits for new cases of breast cancer, and there was a shift towards increased use of telemedicine. Clinical decision-making was largely unaffected in the most aggressive indications (i.e., triple-negative, HER2-positive, visceral crisis). The use of neoadjuvant therapy increased when access to surgery was difficult, whereas dose-dense regimens decreased, and cyclin-dependent kinase 4/6 inhibitor treatment decreased for less aggressive disease and increased for more aggressive disease. The use of oral formulations and metronomic chemotherapy regimens increased, and clinical trial participation decreased. Some differences by respondents’ region and case volume were noted.ConclusionMedical oncologists in Portugal implemented many changes during the COVID-19 pandemic, most of which were logical and reasonable responses to the current healthcare emergency; however, the true impact on patient outcomes remains unknown.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40487-022-00191-7.

Adjuvant cyclin-dependent kinase 4/6 inhibition in hormone receptor-positive breast cancer: One Monarch to rule them all?

The use of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors has dramatically improved outcomes for patients with metastatic, hormone receptor (HR)-positive breast cancer. Because of the continued high rate of relapse in patients with node-positive, HR-positive disease, evaluating these agents in the adjuvant setting is the logical next step. Three adjuvant CDK inhibitor trials have been reported to date, with only 1 of them showing a statistical advantage for the CDK inhibitor in comparison with endocrine therapy alone. These trials have key similarities and differences that could explain the disparate results. The one positive trial has a relatively short follow-up, and continued analysis is critical to confirm the benefit of adjuvant CDK inhibition in this setting. It is imperative that predictive biomarkers be determined so that these agents can be used in the patients most likely to benefit and thus the additional toxicity and expense can be avoided in those who do not require these agents. LAY SUMMARY: There is a critical need for new agents to prevent relapse in patients with hormone receptor-positive breast cancer. Trials to date evaluating cyclin-dependent kinase inhibitors, which decrease how quickly cancer cells multiply, have shown mixed results, with only 1 trial demonstrating that these agents decrease recurrence.

Combination of Talazoparib and Palbociclib as a Potent Treatment Strategy in Bladder Cancer

The use of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors represents a potent strategy for cancer therapy. Due to the complex molecular network that regulates cell cycle progression, cancer cells often acquire resistance mechanisms against these inhibitors. Previously, our group identified molecular factors conferring resistance to CDK4/6 inhibition in bladder cancer (BLCA) that also included components within the DNA repair pathway. In this study, we validated whether a combinatory treatment approach of the CDK4/6 inhibitor Palbociclib with Poly-(ADP-Ribose) Polymerase (PARP) inhibitors improves therapy response in BLCA. First, a comparison of PARP inhibitors Talazoparib and Olaparib showed superior efficacy of Talazoparib in vitro and displayed high antitumor activity in xenografts in the chicken chorioallantoic membrane (CAM) model. Moreover, the combination of Talazoparib and the CDK4/6 inhibitor Palbociclib synergistically reduced tumor growth in Retinoblastoma protein (RB)-positive BLCA in vitro and in a CAM model, an effect that relies on Palbociclib-induced cell cycle arrest in G0/G1-phase complemented by a G2 arrest induced by Talazoparib. Interestingly, Talazoparib-induced apoptosis was reduced by Palbociclib. The combination of Palbociclib and Talazoparib effectively enhances BLCA therapy, and RB is a molecular biomarker of response to this treatment regimen.

ESMO20 YO for YO: highlights on adjuvant CDK4/6 inhibitors in early hormone receptor-positive/HER2-negative breast cancer

ESMO20 virtual conference brought us the results of two major randomized trials on the adjuvant use of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) for early hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative breast cancer (BC). The two studies, PALLAS with palbociclib (ClinicalTrials.gov identifier NCT02513394) and monarchE with abemaciclib (NCT03155997), reported conflicting results. In the latter, adding abemaciclib for 2 years to standard endocrine therapy improved both the primary endpoint, invasive disease-free survival (DFS) with an absolute improvement of 3.5% at 2 years, as well as distant relapse-free survival (DRFS) with an absolute improvement of 3.3% at 2 years.

Concurrent Use of Cyclin Dependent Kinase 4/6 (CDK4/6) Inhibitors with Palliative Radiotherapy for Metastatic Breast Cancer Patients: A Review of Toxicity

Concurrent Use of Cyclin Dependent Kinase 4/6 (CDK4/6) Inhibitors with Palliative Radiotherapy for Metastatic Breast Cancer Patients: A Review of Toxicity

P139: Uptake of Cyclin Dependant Kinase 4/6 inhibitors (CDKi) - A retrospective audit at University Hospital Birmingham trust (UHB) (audit approval number: Carms15507)

Introduction: Since 2017, NICE has approved the first line use of Cyclin Dependent Kinase 4/6 Inhibitors (CDKis) for hormone receptor positive and HER2 negative locally advanced (LABC) or metastatic breast cancer (MBC). Uptake amongst units is variable. CDKis are currently only licensed in conjunction with an aromatase inhibitor or Fulvestrant. Alternative treatments include endocrine monotherapy and/or chemotherapy. This retrospective audit aims to quantify the uptake of CDKis at University Hospital Birmingham (UHB) Trust, and assess variations, if any, compared to the expected uptake of 60% determined by NICE.

Prediction of early progression (EP) to CDKIs first line treatment in ER+/HER2- metastatic breast cancer (MBC) using machine learning.

e13040 Background: The treatment of luminal MBC has undergone a substantial change with the use of cyclin dependent kinase 4/6 inhibitors (CDKIs). Nevertheless, there is not a clearly defined subgroup of patients who do not initially respond to CDKIs and show EP. Methods: MBC ER+/HER2- patients who have received at least one line of treatment were eligible. The event of interest was disease progression within 6 months of first line treatment according to the type of therapy administered. The first line treatments were categorized in chemotherapy (CT), hormonal therapy (HT), CT plus maintenance HT and HT plus CDKIs. Free text data from clinical visits registered in our Electronic Health Record were obtained until the date of first treatment in order to generate a feature vector composed of the word frequencies for each visit of every patient. Six different machine learning algorithms were evaluated to predict the event of interest and to obtain the risk of EP for every type of therapy. Area under the ROC curve (AUC), True Positive Rate (TPR) and True Negative Rate (TNR) were assessed using 10-fold cross validation. Results: 610 RE+/HER2- MBC treated between November 1991 and August 2019 were included. Median follow up for metastatic disease was 28 months. 17426 clinical visits were analyzed (per patient: range 1-173; median 30). 119 patients received CT as first line treatment, 311 HT, 117 CT plus maintenance HT and 63 HT plus CDKIs. There were 379 patients with disease progression, from which 126 were within 6 months from first line treatment (54 events with CT, 57 with HT, 4 with CT plus maintenance HT and 11 with HT plus CDKIs). The model that yields the best results was the GLMBoost algorithm: AUC 0.72 (95%CI 0.67-0.77), TPR 70.85% (95%CI 70.63%-71.06%), TNR 66.27% (95% 66.08%-66.46%). Conclusions: Our model based on unstructured data from real-world patients predicts EP and establishes the risk for each of the different types of treatment for MBC ER+/HER2-. Obviously an additional validation is needed, but a tool with these characteristics could help to select the best available treatment when that decision has to be made, avoiding those therapies that are probably not to be effective.

Characterization of first-line use of cyclin dependent kinase 4/6 (CDK4/6) inhibitors in metastatic breast cancer among Florida health care systems.

e19347 Background: First-line treatment with a CDK4/6 inhibitor in combination with an aromatase inhibitor for HR+/HER2- postmenopausal metastatic breast cancer (mBC) is considered standard of care based on the compelling data across all landmark trials. Commission on Cancer (CoC) as well as the Quality Oncology Practice Initiative (QOPI) describe standards for cancer care; some of which include utilizing data for continuous quality improvement as well as using nationally recognized guidelines to drive treatment selection. Reducing unwarranted variations in care through tracking and reporting adherence to nationally-recognized guidelines can be one way to focus on improving quality metrics. We evaluate first-line real-world treatment patterns of HR+/HER2- mBC patients in three health care systems in south Florida and compare with national standards. Methods: A retrospective analysis utilizing pharmacy and medical claims data (commercial and governmental payers) was performed. The data source was the IQVIA anonymized patient longitudinal open claims data for patients treated at the south Florida health systems. Patients age ≥18 years with HR+/HER2- mBC were included. First-line treatment was defined as the first claim for a medication after the mBC diagnosis. Results: Characterization of treatment patterns in three cancer centers in south Florida showed an increased utilization of CDK4/6 inhibitors as compared to the national average across all groups (see table). Conclusions: These data provide a baseline assessment of the utilization of CDK4/6 inhibitors in the first-line treatment of HR+/HER2- mBC. These data are reassuring with respect to the appropriate treatment in south Florida patients. However, we anticipate that treatment patterns may vary in other geographic areas given the national data trends. We would recommend this data be evaluated in other systems to identify potential areas of improvement. Limitations of this evaluation are consistent with any methodology using claims data which include possible coding errors and missing data which may or may not be systematic. [Table: see text]

175P Real-world patient and practice characteristics associated with use of CDK4/6 inhibitors among patients receiving first therapy for HR+/HER2- advanced or metastatic breast cancer in Italy and Germany

Since approval in 2016, clinical practice guidelines in Europe recommend the use of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy for the treatment of advanced or metastatic breast cancer (a/mBC). Few studies have examined factors associated with use of CDK4/6i therapy. This study aimed to characterize patient and practice characteristics associated with first-line selection of CDK4/6i therapy among patients with a/mBC.

BPI20-022: Use of Cyclin Dependent Kinase 4/6 Inhibitors in Hormone Receptor Positive HER2 Negative Metastatic Breast Cancer. Experience in a Third Level Hospital in Mexico City

"BPI20-022: Use of Cyclin Dependent Kinase 4/6 Inhibitors in Hormone Receptor Positive HER2 Negative Metastatic Breast Cancer. Experience in a Third Level Hospital in Mexico City" published on 20 Mar 2020 by National Comprehensive Cancer Network.

Progression-Free Survival for Real-World Use of Palbociclib in Hormone Receptor-Positive Metastatic Breast Cancer

BackgroundAdditional use of cyclin-dependent kinase 4/6 inhibitors with endocrine therapy improves progression-free survival (PFS) in advanced hormone receptor (HR)-positive HER2-negative breast cancer. However, neutropenia is a common reason for dose reductions, leading to concerns about palbociclib efficacy at lower doses. A safety analysis confirmed no PFS differences between palbociclib doses in the second-line setting, but to our knowledge, this has not been evaluated for first-line treatment. Patients and MethodsIn this retrospective, single-center cohort study we evaluated real-world use of first-line palbociclib with aromatase inhibitor (AI) treatment in HR-positive, HER2-negative metastatic breast cancer patients who received treatment between February 2015 and July 2017. The primary objective was to determine PFS of treatment with palbociclib and an AI in a real-world first-line setting. Secondary objectives included determining the PFS for patients treated with palbociclib on the basis of final doses, time to first dose reduction, time to treatment failure (TTF), and safety. ResultsSeventy patients were included in the final analysis. Median PFS was 26.4 months. No significant differences in PFS were observed on the basis of final doses of palbociclib (P = .77). Time to first dose reduction was 2.3 months. Median TTF was 26.1 months. Dose delays, reductions, and Grade 3/4 neutropenia were common (63%, n = 44; 57%, n = 40; and 62%, n = 43, respectively). ConclusionReal-world first-line palbociclib treatment produced outcomes similar to those in PALOMA-2 (Palbociclib and Letrozole in Advanced Breast Cancer) (median PFS 26.4 months vs. 24.8 months) despite more dose reductions (57%, n = 40 vs. 36%, n = 160) and shorter time to first dose reduction (2.3 vs. 3.0 months). No significant differences in PFS were observed for the varying palbociclib doses. Palbociclib dose reductions might not significantly affect PFS in the first-line setting.

Review of Cyclin-Dependent Kinase 4/6 Inhibitors for the Treatment of Hormone Receptor-Positive Advanced Breast Cancer.

To evaluate the existing literature regarding the use of cyclin-dependent kinase (CDK) 4/6 inhibitors in the treatment of hormone receptor-positive advanced breast cancer (ABC). A search of the medical literature was performed using PubMed (2014 to June 2018). Search terms included cyclin-dependent kinase, CDK, breast cancer, palbociclib, ribociclib, abemaciclib, PD0332991, LEE011, and LY2835219. Clinicaltrials.gov was also searched. Trials with clinical efficacy outcomes evaluating CDK 4/6 inhibitors in the treatment of advanced hormone-positive breast cancer were considered. Palbociclib, abemaciclib, and ribociclib each demonstrated significant benefit when combined with an aromatase inhibitor, the benefit to patients was similar for each, with an improvement of 42% to 51% in median progression-free survival (PFS). In combination with fulvestrant, CDK 4/6 inhibitors used for the treatment of hormone receptor-positive ABC resulted in a 43% to 58% improvement in median PFS versus fulvestrant alone. CDK inhibitors are relatively well tolerated; however, discontinuation as a result of adverse effects was highest with abemaciclib. Relevance to Patient Care and Clinical Practice: This review considers the use of the 3 commercially available CDK 4/6 inhibitors for treatment of hormone receptor-positive breast cancer, including data on each of the 3 agents in newly advanced and treatment refractory disease. The CDK inhibitors should be used in combination with endocrine therapies for the treatment of ABC. Efficacy of the 3 agents is similar. Selection within the class should include consideration of adverse effects and drug interactions.