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

Overall survival results from the randomized phase 2 study of palbociclib in combination with letrozole versus letrozole alone for first‑line treatment of ER+/HER2− advanced breast cancer (PALOMA‑1, TRIO‑18)

Purpose Palbociclib is a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, approved in combination with endocrine therapy for the treatment of women and men with hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer (HR+/HER2− ABC). In the phase 2, open-label, PALOMA-1 trial, palbociclib plus letrozole signifcantly prolonged progression-free survival (PFS) versus letrozole alone (hazard ratio, 0.488; 95% CI 0.319‒0.748; P=0.0004; median PFS, 20.2 vs 10.2 months, respectively) in postmenopausal women with estrogen receptor–positive (ER+)/HER2− ABC. Here, we present the fnal overall survival (OS) and updated safety results. Methods Postmenopausal women with ER+/HER2− ABC were randomized 1:1 to receive either palbociclib (125 mg/day, 3/1 schedule) plus letrozole (2.5 mg/day, continuous) or letrozole alone (2.5 mg/day, continuous). The primary endpoint was investigator-assessed PFS; secondary endpoints included OS and safety. Results A total of 165 patients were randomized. At the data cutof date of December 30, 2016 (median duration of follow-up, 64.7 months), the stratifed hazard ratio for OS was 0.897 (95% CI 0.623–1.294; P=0.281); median OS in the palbociclib plus letrozole and letrozole alone arms was 37.5 and 34.5 months, respectively. The median time from randomization to frst subsequent chemotherapy use was longer with palbociclib plus letrozole than letrozole alone (26.7 and 17.7 months, respectively). The most frequently reported adverse event in the palbociclib plus letrozole arm was neutropenia (any grade, 75%; grade 3 or 4, 59%). Conclusions Palbociclib plus letrozole treatment led to a numerical but not statistically signifcant improvement in median OS. Pfzer Inc (NCT00721409

Real-World Effectiveness of Palbociclib Plus Aromatase Inhibitors in African American Patients With Metastatic Breast Cancer.

BACKGROUND: Disparities 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 METHODS: This 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. RESULTS: Of 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). CONCLUSION: This 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 NUMBER: NCT05361655

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

Many Faces of Openness in Adoption: Perspectives of Adopted Adolescents and Their Parents

Parents and adolescents (mean age, 15.7 years) from 177 adoptive families participating in the second wave of the Minnesota/Texas Adoption Research Project were interviewed about their post-adoption contact arrangements. The sample included families with no contact, stopped contact, contact without meetings, and contact with face-to-face meetings between the adolescent and birth mother. Openness arrangements were dynamic, and different openness arrangements were associated with different experiences and feelings. Adoptive families with contact reported having higher levels of satisfaction about their openness arrangements, experiencing more positive feelings about the birth mother, and possessing more factual and personal knowledge about the birth mother than did families without contact. Adolescents and adoptive mothers in the contact with meetings group reported the greatest satisfaction with their openness arrangements; those with no contact or stopped contact reported the least satisfaction with their arrangements. Participants having no contact were more likely to want the intensity of contact to increase in the future rather than stay the same. Many participants already having contact wanted it to increase in the future. Fewer than 1 percent of all participants wanted to see the intensity of contact decrease

The effect of neutropenia on patient-reported functioning and quality of life (QOL) among palbociclib participants of the MADELINE study

1064 Background: MADELINE is an observational, multicenter study of women with HR+/HER2- advanced or metastatic breast cancer who were followed for 6 months to evaluate patient reported QOL after initiating palbociclib combination therapy or other approved treatment in the US. A novel mobile application was developed to capture PROs for QOL at daily, weekly, monthly/cycle-based intervals for up to 6 months. QOL measures were evaluated to determine if palbociclib-treated patients experiencing episodes of neutropenia had associated decreases in QOL compared to patients without episodes of neutropenia. Methods: Patients completed the SF-12 and CES-D-10 at baseline and each cycle. Change from baseline was assessed using mean scores and mixed-effects models. Daily pain and fatigue severity were measured on an 11-point scale (0-10, 10 being worst possible pain/fatigue) and averaged to create weekly scores. Patients indicated weekly how breast cancer or its treatment interfered with family/social life, productivity, physical activity and energy on a 5-point scales (from not at all to a great deal). Demographic and clinical data including adverse events were recorded in an eCRF. Results: 25 sites contributed 139 patients (median [range] age 60 [34, 82]; white: 83%; ECOG 0-1: 87%). During the 6-month follow up period, 45% of patients experienced ≥1 neutropenia event (grade 1-4: 17%, 27%, 24%, 2%) and 11% had an event resulting in a dose change. Least-square (LS) mean change from baseline to end of study for the SF-12 Physical/Mental Component summaries (PCS/MCS) and the CES-D-10 showed no association between neutropenia and decreased QOL. Daily pain/fatigue was relatively stable for those with neutropenia (cycle 1, week 1: 2.8 [1.95] and 1.8 [0.95]; cycle 6, week 1: 2.4 [1.95] and 2.3 [1.59]) and those without (cycle 1, week 1: 2.2 [2.46] and 2.8 [2.39]; cycle 6, week 1: 1.6 [2.29] and 2.4 [2.22]). There was no significant change for impact of breast cancer or treatment across cycles. Conclusions: Patients with neutropenia did not experience decreased QOL compared to patients without neutropenia nor did patients as a whole experience numerically or clinically meaningful decrease in QOL throughout the follow up period. Daily PROs collected suggest a low level of pain/fatigue that did not change substantially over time. [Table: see text