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

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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Erratum: Corrigendum: Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution

International Chicken Genome Sequencing Consortium. The Original Article was published on 09 December 2004. Nature432, 695–716 (2004). In Table 5 of this Article, the last four values listed in the ‘Copy number’ column were incorrect. These should be: LTR elements, 30,000; DNA transposons, 20,000; simple repeats, 140,000; and satellites, 4,000. These errors do not affect any of the conclusions in our paper. Additional information. The online version of the original article can be found at 10.1038/nature0315

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

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

Histology-based survival outcomes in hormone receptor-positive metastatic breast cancer treated with targeted therapies

Abstract The addition of targeted therapies (TT) to endocrine therapy (ET) has improved the outcomes of patients with HR-positive, HER2-negative metastatic breast cancer (mBC). However, it is unknown whether patients with invasive lobular carcinoma (ILC) or mixed invasive ductal and lobular carcinoma (mixed) histologies experience the same magnitude of benefit from this therapy as those with invasive ductal carcinoma (IDC). We aim to determine whether patients with IDC, ILC, and mixed HR+/HER2− mBC derive similar benefit from the addition of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is), mammalian target of rapamycin inhibitor (mTORi), and phosphoinositide 3-kinase inhibitor (PI3Ki) to ET in HR+/HER2− mBC. We conducted an observational, population-based investigation using data from the MD Anderson prospectively collected database. We conducted a histology-based analysis of progression-free survival (PFS) and overall survival (OS) durations in 3784 patients with HR+/HER2− mBC who were treated with TT plus ET between January 1, 2010, and December 31, 2021. Out of the 3784 patients, 2975 were included in the final analysis. Of these, 2249 received CDK4/6is (81% IDC, 15% ILC, and 4% mixed), 1027 received everolimus (82% IDC, 14% ILC, and 4% mixed) and 49 received alpelisib (81% IDC and 19% ILC). The addition of targeted therapy to ET did not result in statistically significant differences in PFS or OS duration among patients with IDC, ILC, and mixed HR+/HER2− mBC. We concluded that for patients with HR+/HER2− mBC, the addition of TT to ET leads to a similar magnitude of benefit, irrespective of histology

Table_1_Real-world treatment patterns and effectiveness of palbociclib plus an aromatase inhibitor in patients with metastatic breast cancer aged 75 years or older.docx

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

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

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 &lt; 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 &lt; 0.0001). These data support first-line palbociclib plus an AI treatment for HR+/HER2- MBC.(Trial number NCT05361655)