Correction to: Real-World Tumor Response of Palbociclib Plus Letrozole Versus Letrozole for Metastatic Breast Cancer in US Clinical Practice.
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ABSTRACT:
SUBMITTER: Brufsky A
PROVIDER: S-EPMC9172681 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
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Correction to: Real-World Tumor Response of Palbociclib Plus Letrozole Versus Letrozole for Metastatic Breast Cancer in US Clinical Practice.
Brufsky Adam A Liu Xianchen X Li Benjamin B McRoy Lynn L Layman Rachel M RM
Targeted oncology 20211101 6
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Project description:BackgroundLimited information exists regarding tumor response to palbociclib plus an aromatase inhibitor (AI) versus AI alone in real-world practice.ObjectiveTo evaluate the real-world tumor response of palbociclib plus letrozole (PAL+LET) versus LET alone as first-line treatment for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer (HR+/HER2‒ MBC) in routine US clinical practice.Patients and methodsThis retrospective analysis included HR+/HER2‒ MBC patients who initiated PAL+LET or LET as first-line treatment between February 2015 and September 2018 in the Flatiron Health Analytics database. Patients were followed until December 2018. Real-world best tumor response (rwBTR) was determined based on physicians' assessment of radiologic evidence for change in burden of disease.ResultsOf the 1383 eligible patients who initiated PAL+LET or LET as first-line therapy in the Flatiron database, 968 patients had ≥ 1 tumor response assessment (662 received PAL+LET and 306 received LET). The rwBTR rate (complete response+partial response) in the first-line setting was 59.8% in the PAL+LET group and 39.2% in the LET group (odds ratio 2.31 (95% CI 1.75‒3.04), P < 0.0001). After 1:1 propensity-score matching, the rwBTR rate was 58.6% in the PAL+LET group versus 39.1% in the LET group (odds ratio 2.21 (95% CI 1.50‒3.25), P < 0.0001).ConclusionsThis real-world analysis demonstrated that HR+/HER2‒ MBC patients were more likely to respond to PAL+LET compared to LET. These findings further showed the effectiveness of PAL+LET therapy in the real-world setting and support the combination as a standard of care for MBC.Study registrationPfizer; NCT04176354; registered November 25, 2019.
| S-EPMC8484164 | biostudies-literature
Project description:BackgroundFindings from randomized clinical trials may have limited generalizability to patients treated in routine clinical practice. This study examined the effectiveness of first-line palbociclib plus letrozole versus letrozole alone on survival outcomes in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor-negative (HER2-) metastatic breast cancer (MBC) treated in routine clinical practice in the USA.Patients and methodsThis was a retrospective observational analysis of electronic health records within the Flatiron Health Analytic Database. A total of 1430 patients with ≥ 3 months of follow-up received palbociclib plus letrozole or letrozole alone in the first-line setting between February 3, 2015, and February 28, 2019. Stabilized inverse probability treatment weighting (sIPTW) was used to balance baseline demographic and clinical characteristics. Real-world progression-free survival (rwPFS) and overall survival (OS) were analyzed.ResultsAfter sIPTW adjustment, median follow-up was 24.2 months (interquartile range [IQR], 14.2-34.9) in the palbociclib group and 23.3 months (IQR, 12.7-34.3) in those taking letrozole alone. Palbociclib combination treatment was associated with significantly longer median rwPFS compared to letrozole alone (20.0 vs 11.9 months; hazard ratio [HR], 0.58; 95% CI, 0.49-0.69; P < 0.0001). Median OS was not reached in the palbociclib group and was 43.1 months with letrozole alone (HR, 0.66; 95% CI, 0.53-0.82; P = 0.0002). The 2-year OS rate was 78.3% in the palbociclib group and 68.0% with letrozole alone. A propensity score matching analysis showed similar results.ConclusionsIn this "real-world" population of patients with HR+/HER2- MBC, palbociclib in combination with endocrine therapy was associated with improved survival outcomes compared with patients treated with letrozole alone in the first-line setting.Trial registrationClinicaltrials.gov; NCT04176354.
| S-EPMC7989035 | biostudies-literature
Project description: Not available
| S-EPMC10398120 | biostudies-literature
Project description:BackgroundDisparities in survival and clinical outcomes between African American and White patients with breast cancer (BC) are well documented, but African American patients have not been well represented in randomized clinical trials of CDK4/6 inhibitors. Real-world studies can provide evidence for effective treatment strategies for underreported patient populations.Patients and methodsThis retrospective analysis of African American patients with HR+/HER2- metastatic breast cancer (mBC) from the Flatiron Health longitudinal database evaluated treatments for patients with BC in routine clinical practice in the US. Patients initiated first-line therapy with palbociclib plus an aromatase inhibitor (AI) or AI alone between February 2015 and March 2020. Outcomes assessed included overall survival (OS) and real-world progression-free survival (rwPFS) until September 2020.ResultsOf 270 eligible patients, 127 (median age 64 years) were treated with palbociclib + AI, and 143 (median age 68 years) were treated with an AI. Median follow-up was 24.0 months for palbociclib + AI and 18.2 months for AI-treated patients. Median OS was not reached (NR; 95% CI, 38.2-NR) in the palbociclib + AI group versus 28.2 months (95% CI, 19.2-52.8) in the AI group (adjusted HR, 0.56; 95% CI, 0.36-0.89; P = .013). Median rwPFS was 18.0 months (95% CI, 12.4-26.7) in the palbociclib + AI group and 10.5 months (95% CI, 7.0-13.4) in the AI group (adjusted HR, 0.74; 95% CI, 0.47-1.17; P = .199).ConclusionThis comparative analysis of palbociclib + AI versus AI alone indicates that palbociclib combined with endocrine therapy in the first line is associated with improved effectiveness for African American patients with HR+/HER2- mBC in real-world settings.Trial numberNCT05361655.
| S-EPMC10546832 | biostudies-literature
Project description:Data on real-world effectiveness of cyclin-dependent kinase 4/6 inhibitor combination therapy versus endocrine therapy 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 with first-line palbociclib plus an aromatase inhibitor (AI) versus an AI alone in routine US clinical practice. In total, 2888 patients initiated treatment during February 3, 2015-March 31, 2020, with a potential ≥6-month follow-up (cutoff date, September 30, 2020). After stabilized inverse probability treatment weighting, median OS (95% CI) is significantly longer among palbociclib versus AI recipients (49.1 [45.2-57.7] versus 43.2 [37.6-48.0] months; hazard ratio, 0.76 [95% CI, 0.65-0.87]; P < 0.0001). Progression-free survival (95% CI) is 19.3 (17.5-20.7) versus 13.9 (12.5-15.2) months, respectively (hazard ratio, 0.70 [95% CI, 0.62-0.78]; P < 0.0001). These data support first-line palbociclib plus an AI treatment for HR+/HER2- MBC.(Trial number NCT05361655).
| S-EPMC9553912 | biostudies-literature
Project description:BackgroundThe global burden of breast cancer (BC) is high, especially in advanced stages. CDK 4/6 inhibitors represent a paradigm shift in the treatment of advanced BC HR+/HER2-, given the clinically and statistically significant gain in overall survival associated with this new class of medications. Nevertheless, as an innovation, the incorporation of these drugs impacts healthcare budgets, requiring cost-effectiveness analyses for decision-making. The aim of this study was to evaluate the cost-effectiveness of ribociclib plus letrozole compared with palbociclib plus letrozole or letrozole as monotherapy for first-line treatment of postmenopausal women with HR+/HER2- locally advanced or metastatic BC (aBC) from a Brazilian private healthcare system perspective.MethodsA model including progression-free survival (PFS), progressed disease, and death health states was used to simulate lifetime costs and outcomes. PFS and overall survival were derived from the MONALEESA-2 trial (lifetime horizon). Healthcare costs included drug acquisition and monitoring, subsequent therapies, adverse events, and end-of-life costs. Effectiveness was measured in quality-adjusted life-years (QALYs). Deterministic and probabilistic sensitivity analyses were performed.ResultsThe total cost of treatment with ribociclib plus letrozole was USD 72,091.82 versus USD 92,749.64 for palbociclib plus letrozole. Total QALYs were 3.30 and 3.16, respectively. Base-case analysis showed ribociclib as dominant over palbociclib in first-line treatment of women with HR+/HER2- aBC, associated with cost savings and QALY gains. The total cost of treatment with ribociclib plus letrozole was USD 83,058.73 versus USD 29,215.10 for letrozole. Total QALYs were 3.84 and 2.61, respectively. Compared with letrozole, ribociclib plus letrozole was associated with an incremental cost of USD 53,843.64 and an incremental QALY gain of 1.23, with incremental cost-effectiveness ratio of USD 43,826.91 per QALY gained.ConclusionsAs demonstrated by the cost-effectiveness dominance over palbociclib, ribociclib results in savings when used as first-line treatment in postmenopausal women with HR+/HER2- aBC, warranting incorporation in the private healthcare system.
| S-EPMC8053836 | biostudies-literature
Project description:Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.PALOMA-2 demonstrated statistically and clinically significant improvement in progression-free survival with palbociclib plus letrozole versus placebo plus letrozole in estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer (ABC). Here, we report results for the secondary end point overall survival (OS). Postmenopausal women (N = 666) with ER+/HER2- ABC without previous systemic therapy for ABC were randomly assigned 2:1 to palbociclib plus letrozole or placebo plus letrozole. After a median follow-up of 90.1 months, 405 deaths were observed and 155 patients were known to be alive. The median OS was 53.9 months (95% CI, 49.8 to 60.8) with palbociclib plus letrozole versus 51.2 months (95% CI, 43.7 to 58.9) with placebo plus letrozole (hazard ratio [HR], 0.96 [95% CI, 0.78 to 1.18]; stratified one-sided P = .34). An imbalance in the number of patients with unknown survival outcome between the treatment arms (13.3% v 21.2%, respectively) limited interpretation of OS results. With recovered survival data, the median OS was 53.8 (95% CI, 49.8 to 59.2) versus 49.8 months (95% CI, 42.3 to 56.4), respectively (HR, 0.92 [95% CI, 0.76 to 1.12]; one-sided P = .21). OS was not significantly improved with palbociclib plus letrozole compared with placebo plus letrozole.
| S-EPMC10950136 | biostudies-literature
Project description:BackgroundFor 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 the occurrence of ESR1 mutations, selective estrogen receptor modulators or degraders (SERDs) may be used, alone or in combination regimens. Amcenestrant (SAR439859), an optimized oral SERD, has shown clinical antitumor activity in combination with palbociclib in patients with ER+/HER2- ABC and, as monotherapy, in patients with and without ESR1 mutations. Here, we describe the study design of AMEERA-5, an ongoing, prospective, phase 3, randomized, double-blind, multinational study comparing the efficacy and safety of amcenestrant plus palbociclib versus letrozole plus palbociclib in patients with advanced (locoregional recurrent or metastatic) ER+/HER2- breast cancer.MethodsPatients are pre-/postmenopausal women and men with no prior systemic therapy for ABC. The planned enrollment is 1066 patients. Patients are randomized 1:1 to either amcenestrant 200 mg plus palbociclib 125 mg or letrozole 2.5 mg plus palbociclib 125 mg. Amcenestrant, letrozole, and their matching placebos are taken once daily continuously; palbociclib is taken once daily for 21 days, followed by 7 days off-treatment for a 28-day cycle. Treatment continues until disease progression, unacceptable toxicity, or decision to stop treatment. Pre-/perimenopausal women and men receive goserelin subcutaneously. Randomization is stratified by de novo metastatic disease, menopausal status, and visceral metastases. The primary endpoint is progression-free survival. The key secondary endpoint is overall survival; others are safety, pharmacokinetics, and quality of life.ConclusionsAMEERA-5 is evaluating the efficacy and safety of amcenestrant in combination with palbociclib as first-line therapy in pre-/postmenopausal women and men with ER+/HER2- ABC.Clinicaltrials identifierNCT04478266.
| S-EPMC8928355 | biostudies-literature
Project description:BackgroundCurrent standard-of-care first-line treatment of patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC) is cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) + endocrine therapy. In the MONALEESA-2 trial, first-line ribociclib + letrozole demonstrated statistically significant overall survival (OS) benefit versus placebo + letrozole in postmenopausal patients with HR+/HER2- ABC. In the PALOMA-2 trial, first-line palbociclib + letrozole did not show OS benefit versus placebo + letrozole in a similar patient population. Understanding OS outcomes in the respective trials is critical for treatment decisions; however, there are no head-to-head clinical trial data comparing ribociclib and palbociclib.ObjectivesTo conduct a matching-adjusted indirect comparison (MAIC) to compare progression-free survival (PFS) and OS of first-line ribociclib + letrozole versus palbociclib + letrozole in postmenopausal patients with HR+/HER2- ABC.DesignLetrozole-anchored MAIC using individual patient data from MONALEESA-2 and published summary data from PALOMA-2.MethodsUsing individual data, patients from MONALEESA-2 who matched inclusion criteria from PALOMA-2 were selected, and weighting was conducted to ensure baseline characteristics were similar to those in published aggregated data from PALOMA-2. The Bucher method was used to generate corresponding hazard ratios (HRs).ResultsThe final effective sample size compared n = 150 (ribociclib) and n = 112 (placebo) MONALEESA-2 patients with n = 444 (palbociclib) and n = 222 (placebo) PALOMA-2 patients. After matching and weighting, patient characteristics were well balanced. MAIC analysis showed a numerical PFS benefit [HR, 0.80; 95% confidence interval (CI), 0.58-1.11; p = 0.187] and significant OS benefit (HR, 0.68; 95% CI, 0.48-0.96; p = 0.031) with ribociclib + letrozole versus palbociclib + letrozole.ConclusionResults of this cross-trial MAIC analysis showed a numerical PFS benefit and significantly greater OS benefit with first-line ribociclib + letrozole versus palbociclib + letrozole. These results support letrozole + ribociclib as the preferred first-line CDK4/6i for postmenopausal patients with HR+/HER2- ABC.Trial registrationNCT01958021; https://www.clinicaltrials.gov/study/NCT01958021 (MONALEESA-2) and NCT01740427; https://clinicaltrials.gov/study/NCT01740427 (PALOMA-2).
| S-EPMC10722948 | biostudies-literature
Project description: Not available
| S-EPMC10569486 | biostudies-literature