Comparative overall survival of CDK4/6 inhibitors plus an aromatase inhibitor in HR+/HER2− metastatic breast cancer in the US real-world setting

ESMO Open, Journal Year: 2025, Volume and Issue: 10(1), P. 104103 - 104103

Published: Jan. 1, 2025

Randomized controlled trials have shown inconsistent overall survival (OS) benefit among the three cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) as first-line (1L) treatment of patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC). Several real-world studies compared CDK4/6i effectiveness, findings. This study HR+/HER2- mBC receiving 1L palbociclib, ribociclib, or abemaciclib, in combination an aromatase inhibitor (AI), US clinical practice.

Language: Английский

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

Targeted Oncology, Journal Year: 2024, Volume and Issue: 19(3), P. 303 - 320

Published: March 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.

Language: Английский

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Real-world treatment patterns and effectiveness of palbociclib plus an aromatase inhibitor in patients with metastatic breast cancer aged 75 years or older

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: Sept. 28, 2023

Elderly patients are generally underrepresented in oncology clinical trials; therefore, real-world data needed to inform management of elderly with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC). This subanalysis the P-REALITY X study (NCT05361655) evaluated palbociclib treatment patterns and comparative effectiveness plus an aromatase inhibitor (AI) versus AI alone among HR+/HER2- mBC aged ≥ 75 years treated routine practice United States.This retrospective observational cohort used electronic health records from Flatiron Health Analytic Database. Palbociclib patterns, overall survival (OS), progression-free (rwPFS), time chemotherapy (TTC) were evaluated. Three methods for analyses: (1) unadjusted analysis, (2) stabilized inverse probability weighting (sIPTW; primary analysis), (3) propensity score matching (PSM; sensitivity analysis).A total 961 identified who started (n = 313) or 648) as first-line (1L) therapy between February 2015 March 2020 (data cut-off: September 30, 2020). Among group a documented starting dose 306), approximately 75% at 125 mg/day, 40% experienced adjustment. After sIPTW, had significantly improved OS (median 43.0 vs. 32.4 months; hazard ratio [HR], 0.66 [95% confidence interval (CI), 0.51-0.84]; P 0.0007), rwPFS 20.0 15.0 HR, 0.72 (0.59-0.89); 0.0021), TTC 40.2 27.4 0.69 [0.55-0.87]; 0.0014). These significant improvements OS, rwPFS, remained consistent analysis after PSM.This demonstrated that 1L is associated compared years. findings support standard-of-care mBC.

Language: Английский

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Tolerability and effectiveness of palbociclib in older women with metastatic breast cancer

Breast Cancer Research and Treatment, Journal Year: 2024, Volume and Issue: 206(2), P. 337 - 346

Published: April 16, 2024

Abstract Purpose Palbociclib has become the standard of care for estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer, but real-world evidence in older women remains scarce. Therefore, we investigated tolerability palbociclib with cancer. Methods Consecutive aged ≥ 70 ER+/HER2- treated any treatment line six hospitals, were included. Primary endpoint was grade 3 palbociclib-related toxicity. Predictors toxicity identified using logistic regression models. Progression-free survival (PFS) and overall (OS) estimated Kaplan Meier. Results We included 144 a median age 74 years. Grade 3–4 occurred 54% patients, which neutropenia (37%) most common. No neutropenic fever or 5 occurred. Dose reduction during 50% 8% discontinued due to 3% hospitalized Polypharmacy (odds ratio (OR) 2.50; 95% confidence interval (CI) 1.12–5.58) pretreatment low leukocytes (OR 4.81; CI 1.27–18.21) associated toxicity, while comorbidities not. In first-line systemic therapy, PFS 12 months OS 32 months. second-line, 31 Conclusion Although dose reductions frequently, expected managed by reductions, showing that is generally well tolerated thus represents valuable option population.

Language: Английский

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Palbociclib in adults aged 70 years and older with advanced breast cancer: A phase 2 multicenter trial (Alliance A171601)

Journal of Geriatric Oncology, Journal Year: 2024, Volume and Issue: 15(6), P. 101813 - 101813

Published: June 8, 2024

Language: Английский

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Real-world effectiveness of CDK4/6i in first-line treatment of HR+/HER2− advanced/metastatic breast cancer: updated systematic review

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: March 10, 2025

Aim Since 2021, additional real-world evidence (RWE) has emerged on the effectiveness of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) as first-line treatment HR-positive/HER2-negative (HR+/HER2−) advanced/metastatic breast cancer (A/MBC), necessitating this updated review. Methods MEDLINE ® , Embase and Cochrane Databases (07/06/2019–01/09/2024), key congresses (2020–2024) were searched. Studies reporting CDK4/6i use, over 100 participants, progression-free survival (PFS) and/or overall (OS) data included. Results This update included 82 unique studies, 42.7% for palbociclib, 7.3% ribociclib, 3.7% abemaciclib; 46.3% assessed multiple CDK4/6i. In studies including CDK4/6is, median PFS was 23.4–31.0 months 19.8–44.0 14.0–39.5 abemaciclib. When reached, OS 38.0–58.0 months, 40.4–52.0 34.4 respectively. These results within range single-arm versus endocrine therapy (ET) where demonstrated greater benefits than ET alone. Conclusion First-line RWE demonstrates significant clinical in HR+/HER2− A/MBC. are important to guide decision-making, they include patients who not adequately represented trials. with longer follow-up needed assess long-term all three therapies

Language: Английский

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Overall Survival With Palbociclib and Aromatase Inhibitor Versus Aromatase Inhibitor Alone in Older Patients With HR+/HER2− Metastatic Breast Cancer

Cancer Medicine, Journal Year: 2025, Volume and Issue: 14(7)

Published: March 27, 2025

ABSTRACT Introduction Cyclin‐dependent kinase 4/6 inhibitors (CDK4/6is) in combination with endocrine therapy are the current standard of care for first‐line (1L) treatment hormone receptor–positive and human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (mBC). To investigate effectiveness palbociclib, first‐in‐class CDK4/6i, plus an aromatase inhibitor (AI) older patients, we compared overall survival (OS) a Medicare population treated 1L palbociclib + AI versus alone. Methods Patients aged ≥ 65 years who were diagnosed de novo HR+/HER2– mBC from 2015 to 2019 identified Surveillance, Epidemiology, End Results (SEER)–linked database eligible if they initiated or The primary endpoint was OS. Stabilized inverse probability weighting (sIPTW) used balance baseline patient characteristics. Of 779 296 received 483 alone as treatment. After sIPTW, median follow‐up 23.1 months 18.2 Adjusted OS longer (sIPTW: 37.6 vs. 25.5 months, HR = 0.73 [95% CI, 0.59–0.91]). In multivariable Cox proportional hazards regression, patients had 39% lower risk death (HR 0.61 0.48–0.77]). Conclusion routine US clinical practice, associated significantly prolonged mBC, adding growing body evidence on benefit this population. Trial Registration ClinicalTrials.gov identifier: NCT06086340

Language: Английский

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Real-world experience with CDK4-6 inhibition in the old and oldest old with a diagnosis of breast cancer

Seminars in Oncology, Journal Year: 2024, Volume and Issue: 51(3-4), P. 95 - 105

Published: Feb. 22, 2024

Language: Английский

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Real-world treatment patterns and outcomes in patients with HR+/HER2− metastatic breast cancer treated with chemotherapy in the United States

ESMO Open, Journal Year: 2024, Volume and Issue: 9(9), P. 103691 - 103691

Published: Sept. 1, 2024

Language: Английский

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Disparities in receipt of 1-st line CDK4/6 inhibitors with endocrine therapy for treatment of hormone receptor positive, HER2 negative metastatic breast cancer in the real-world setting

Breast Cancer Research, Journal Year: 2024, Volume and Issue: 26(1)

Published: Oct. 18, 2024

This study used real-world observational data to compare profiles of patients receiving different first-line treatment for hormone receptor positive (ER+), HER2 negative, metastatic breast cancer (MBC): CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) versus ET alone. From a nationwide electronic health record-derived Flatiron Health de-identified database including 280 US clinics, we identified positive, 1st -line alone or CDK4/6i plus between February 2015 and November 2021. Patient sociodemographic status, MBC regimen outcomes were the focus this analysis. characteristics compared using t-tests chi-square tests. Logistic regression analysis was performed examine association patient likelihood vs. Kaplan-Meier method Cox proportional hazards test impact on progression-free survival (PFS) overall (OS). Baseline balanced inverse probability weighting (IPW). The population included 3,917 (n = 2170) 1747) their MBC. Compared alone, those younger (mean age 66.8 68.6, p < 0.001), more likely present de novo (p had better performance status (50.2% 40.5% ECOG value 0, 0.001) lower number comorbidities (29.7% 26.6% ≥ 1 comorbidity, 0.001). revealed increased odds individuals aged 50–64 (OR: 3.42, 95% CI [2.41, 4.86]) 65–74 3.18, [1.68, 6.02]) 18–49 years age. Black 0.76, [0.58, 1.00]) White individuals. Other associated stage III disease 0.69, [0.52, 0.92]), 0.50, [0.40, 0.62]), Medicare insurance 0.73, [0.30, 1.78]) commercial Medicaid insurance. After IPW adjustment, use as significantly longer median PFS (27 17 months; hazard ratio [HR] 0.61, Median OS 52 months group 42 (HR 0.74, In database, disparities seen by age, diagnosis stage, baseline status. adjusted analysis, yielded rates than Further efforts are essential enhance equitable access crucial drug class.

Language: Английский

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