Real-world study of overall survival with palbociclib plus aromatase inhibitor in HR+/HER2− metastatic breast cancer

npj Breast Cancer, Год журнала: 2022, Номер 8(1)

Опубликована: Окт. 11, 2022

Data on real-world effectiveness of cyclin-dependent kinase 4/6 inhibitor combination therapy versus endocrine alone are limited. The Flatiron Health Analytic Database was used to assess overall survival (OS) in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC) treated first-line palbociclib plus an aromatase (AI) AI routine US clinical practice. In total, 2888 initiated treatment during February 3, 2015-March 31, 2020, a potential ≥6-month follow-up (cutoff date, September 30, 2020). After stabilized inverse probability weighting, median OS (95% CI) is significantly longer among recipients (49.1 [45.2-57.7] 43.2 [37.6-48.0] months; hazard ratio, 0.76 [95% CI, 0.65-0.87]; P < 0.0001). Progression-free 19.3 (17.5-20.7) 13.9 (12.5-15.2) months, respectively (hazard 0.70 0.62-0.78]; These data support for HR+/HER2- MBC.(Trial number NCT05361655).

Язык: Английский

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Exploring the real-world experience of abemaciclib treatment for HR +, HER2 − metastatic breast cancer—a qualitative analysis of the IMPACTOR study

Supportive Care in Cancer, Год журнала: 2025, Номер 33(5)

Опубликована: Апрель 26, 2025

Abstract Purpose The IMPACTOR study (IMPact of AbemaCiclib on patienTs’ rOles and Responsibilities–ISRCTN17281696) was developed to capture experiences women with MBC being treated abemaciclib in a real-world setting. primary aim explore changes quality life over time our secondary understand these detail via qualitative interviews, as presented here. Methods A singular interview offered participants who had expressed an interest at the point consent. These were all conducted remotely using semi-structured topic guide. Results Twenty interviews completed analysed framework approach thematic analysis. Eight themes developed—COVID-19, experience MBC, side effects, effect management, treatment information support, relationship impacts, impact daily life, finances employment. Conclusions It apparent that faced effects from but undertook steps manage much possible. Adaptations often led by belief about benefits remaining treatment. Adjustments ranged modifying routines carrying personal hygiene supplies when out public case diarrhoea. While this anticipated, other less well known variable clinical support available information. Family raised frequently, predominantly relation roles relationships. Themes work can be thought theories adherence, such common-sense self-regulation models, reflected both emotional cognitive coping strategies. Trial registration - ISRCTN17281696.

Язык: Английский

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Real-world comparative effectiveness of palbociclib plus letrozole versus letrozole in older patients with metastatic breast cancer

The Breast, Год журнала: 2023, Номер 69, С. 375 - 381

Опубликована: Март 27, 2023

Palbociclib, the first available cyclin-dependent kinase 4/6 inhibitor, plus endocrine therapy is approved for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC). This study compared real-world effectiveness of palbociclib letrozole versus in older patients with MBC US clinical practice.This retrospective analysis included from Flatiron Health longitudinal database. Overall, 796 women HR+/HER2- aged ≥65 years starting or as first-line between February 2015 and September 2018 were included. Patients evaluated treatment start until December 2018, death, last visit, whichever came first. Real-world progression-free survival (rwPFS), overall (OS), best tumor responses (rwBTR) endpoints. Stabilized inverse probability weighting (sIPTW) balanced patient characteristics.After sIPTW, 450 treated 335 included; median age was 74.0 years. Median rwPFS 22.2 (95% CI, 20.0-30.4) months 15.8 (12.9-18.9) (hazard ratio, 0.59 [0.47-0.74]; P<0.001). OS not reached 43.4 (30.0-not estimable) 0.55 [0.42-0.72]; No interactions groups (65-74 ≥75 years) observed OS. Rate rwBTR significantly higher (52.4%) (22.1%; odds 2.0 [1.4-2.7]; P<0.001).This demonstrates combination standard-of-care setting.

Язык: Английский

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Palbociclib in Older Patients with Advanced/Metastatic Breast Cancer: A Systematic Review

Targeted Oncology, Год журнала: 2024, Номер 19(3), С. 303 - 320

Опубликована: Март 28, 2024

Palbociclib in combination with endocrine therapy is approved for treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer. In addition to clinical trials, several real-world studies have evaluated the effectiveness palbociclib. With increased life expectancy general population, cancer older women also expected increase. The aim was systematically review evidence from both trials and palbociclib outcomes patients HR+/HER2− advanced/metastatic (a/mBC). Older are often underrepresented (RWE) will enrich analysis this subgroup patients. A systematic literature search PubMed, EMBASE, Cochrane Library through May 4, 2023, yielded 2355 unique articles. total 52 articles (13 39 reporting results seven randomized controlled [RCTs] 37 RWE studies, respectively) were included based on study eligibility criteria. All RCTs used age cutoffs ≥ 65 years define population (n = 722; 437 received palbociclib); all except one an cutoff > 60 years, had or higher 9840; 7408 palbociclib). Overall, that compared efficacy (progression-free survival [seven RCTs, 20 studies], overall [four 11 tumor response [three benefit rate [one RCT, two studies]) safety (three three studies) between younger patients, showed similar benefits, regardless age. Results global quality (QoL) maintained receiving dose modifications (two studies), reductions (one discontinuation rates patients; however, these differences did not appear adversely impact outcomes. review, data effective, well tolerated, QoL a/mBC. settings associated as RCTs. CRD42023444195.

Язык: Английский

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CDK4/6 inhibitors in drug-induced liver injury: a pharmacovigilance study of the FAERS database and analysis of the drug–gene interaction network

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Апрель 3, 2024

Objective: The aim of this study was to investigate the potential risk drug-induced liver injury (DILI) caused by CDK4/6 inhibitors (CDK4/6is abemaciclib, ribociclib, and palbociclib comprehensively analyzing FDA Adverse Event Reporting System (FAERS) database. Moreover, toxicological mechanisms CDK4/6is-related were explored via drug–gene network analysis. Methods: In retrospective observational study, we collected reports DILI associated with CDK4/6i use from FAERS dated January 2014 March 2023. We conducted disproportionality analyses using reporting odds ratio (ROR) a 95% confidence interval (CI). Pathway enrichment analysis drug-gene subsequently performed determine underlying CDK4/6i-induced injury. Results: found positive signals for ribociclib (ROR = 2.60) abemaciclib 2.37). DILIs liver-related investigations, signs, symptoms confirmed in all three CDK4/6is. ascites identified as an unlisted hepatic adverse effect palbociclib. isolated 189 interactive target genes linking Several key genes, such STAT3, HSP90AA1, EP300, revealed protein-protein analysis, emphasizing their central roles within network. KEGG pathway these highlighted multiple pathways. Conclusion: Our variations hepatobiliary toxicity among different inhibitors, showing highest injury, followed while appeared relatively safe. findings emphasize need cautious regular function monitoring is recommended long-term inhibitor use.

Язык: Английский

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Estrogen signaling suppresses tumor-associated tissue eosinophilia to promote breast tumor growth

Science Advances, Год журнала: 2024, Номер 10(39)

Опубликована: Сен. 27, 2024

Estrogens regulate eosinophilia in asthma and other inflammatory diseases. Further, peripheral tumor-associated tissue (TATE) predicts a better response to immune checkpoint blockade (ICB) breast cancer. However, how if estrogens affect eosinophil biology tumors this influences ICB efficacy has not been determined. Here, we report that decrease the number of eosinophils TATE, contributes increased tumor growth validated murine models cancer melanoma. Moreover, estrogen signaling healthy female mice also suppressed prevalence by decreasing proliferation survival maturing eosinophils. Inhibiting receptor (ER) decreased an eosinophil-dependent manner. ICBs was when administered combination with anti-estrogens. These findings highlight importance ER as regulator TATE potential near-term clinical application modulators increase multiple types.

Язык: Английский

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AMEERA-5: a randomized, double-blind phase 3 study of amcenestrant plus palbociclibversusletrozole plus palbociclib for previously untreated ER+/HER2– advanced breast cancer

Therapeutic Advances in Medical Oncology, Год журнала: 2022, Номер 14

Опубликована: Янв. 1, 2022

For estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC), the current standard first-line treatment includes an aromatase inhibitor in combination with a cyclin-dependent kinase 4/6 inhibitor. When resistance occurs, often related to occurrence of ESR1 mutations, selective modulators or degraders (SERDs) may be used, alone regimens. Amcenestrant (SAR439859), optimized oral SERD, has shown clinical antitumor activity palbociclib patients ER+/HER2- ABC and, as monotherapy, and without mutations. Here, we describe study design AMEERA-5, ongoing, prospective, phase 3, randomized, double-blind, multinational comparing efficacy safety amcenestrant plus versus letrozole (locoregional recurrent metastatic) cancer.Patients are pre-/postmenopausal women men no prior systemic therapy for ABC. The planned enrollment is 1066 patients. Patients randomized 1:1 either 200 mg 125 2.5 mg. Amcenestrant, letrozole, their matching placebos taken once daily continuously; 21 days, followed by 7 days off-treatment 28-day cycle. Treatment continues until disease progression, unacceptable toxicity, decision stop treatment. Pre-/perimenopausal receive goserelin subcutaneously. Randomization stratified de novo metastatic disease, menopausal status, visceral metastases. primary endpoint progression-free survival. key secondary overall survival; others safety, pharmacokinetics, quality life.AMEERA-5 evaluating ABC.NCT04478266.

Язык: Английский

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A systematic review of health-related quality of life outcomes in patients with advanced breast cancer treated with palbociclib

Journal of Comparative Effectiveness Research, Год журнала: 2024, Номер 13(10)

Опубликована: Сен. 17, 2024

Aim: To evaluate the impact of palbociclib treatment on health-related quality life (HRQoL) in patients with hormone receptor-positive, human epidermal growth factor 2-negative advanced breast cancer (HR+/HER2- aBC) or metastatic (mBC) both clinical and real-world setting. Materials & methods: A systematic literature review was conducted to identify trials evidence studies up June 2023 that reported HRQoL outcomes HR+/HER2- aBC mBC treated Palbociclib. Results: 15 unique across 35 records were identified. Of these, seven randomized controlled (RCTs), three single-arm five (RWE) studies. generally found be maintained RCTs, RWE measures instruments, study types line therapy, largely at least if not improved from baseline among observed comparable better group versus monotherapy control arm RCTs. Similar results seen for treatment-related (e.g., sexual functioning, upset by hair loss, systemic therapy side effects etc.), important individual patient outcomes, including pain, fatigue physical functioning. Findings also consistent key characteristics (visceral metastases, neutropenia), as well populations often underrepresented (Asian patients, older adults). Conclusion: Overall, current suggests is preserved addition endocrine populations.

Язык: Английский

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Implementation of CDK4/6 Inhibitors and its Influence on the Treatment Landscape of Advanced Breast Cancer Patients – Data from the Real-World Registry PRAEGNANT

Geburtshilfe und Frauenheilkunde, Год журнала: 2022, Номер 82(10), С. 1055 - 1067

Опубликована: Июль 12, 2022

Abstract Background Comprehensive data from prospective clinical trials have led to a high level of evidence establishing CDK4/6 inhibitors in combination with endocrine treatment (CDK4/6i + ET) as standard for the HER2-negative, hormone receptor-positive (HER2− HR+) breast cancer patients first-line advanced therapy setting. Data on patient populations that been treated real-world setting may provide an insight into changes characteristics and prognosis over time. Methods The were extracted registry PRAEGNANT (NCT02338167). Patients had HER2− HR+ metastatic chosen therapies described well progression-free survival (PFS) overall (OS) relation given time periods during which they indicated. Results rapidly implemented since their introduction November 2016. In recent years (2018 – 2022), about 70 80% population inhibitors, while monotherapy was 10% chemotherapy 15% all patients. worst chemotherapy. Recently, mainly good are being monotherapy, who unfavorable prognosis. PFS OS CDK4/6i ET remained similar despite characteristics. Conclusion A has become After implementation ET, is only very favorable prognosis, provided rather These did not seem influence ET.

Язык: Английский

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Treatment efficacy of ribociclib or palbociclib plus letrozole in hormone receptor-positive/HER2-negative metastatic breast cancer

Future Oncology, Год журнала: 2023, Номер 19(10), С. 727 - 736

Опубликована: Март 1, 2023

Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase as the first-line standard-of-care for patients hormone receptor-positive, HER2-negative metastatic breast cancer.

Язык: Английский

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