This retrospective single-arm study assessed real-world treatment patterns and clinical outcomes in patients with hormone receptor—positive/human epidermal growth factor receptor 2—negative (HR+/HER2−) advanced/metastatic breast cancer (A/MBC) who received palbociclib plus an aromatase inhibitor as first-line therapy in US community health systems. Using electronic health records from the Syapse Learning Health Network, 242 patients were identified as having received first-line palbociclib plus an aromatase inhibitor between 3 February 2015, and 31 July 2019 (data cutoff 1 February 2020) resulting in a minimum potential 6-month follow-up period. In total, 56.6% of patients had de novo A/MBC at initial breast cancer diagnosis, 50.8% had bone-only disease, and 32.2% had visceral disease. Median follow-up was 22.4 months. Disease progression (26.4%) and intolerance/toxicity (14.9%) were the main reasons for treatment discontinuation. The median (95% CI) real-world progression-free survival was 31.7 (27.9—not estimable (NE)) months and 2-year estimated overall survival (OS) rate was 78.0%. In total, 25.6% of patients died; however, OS data are limited by the small population size and insufficient follow-up time. These real-world effectiveness outcomes complement findings from other real-world studies and randomized controlled trials and support palbociclib plus an aromatase inhibitor as first-line therapy for HR+/HER2− A/MBC.
Background While HIV programmes have started millions of persons on life-saving antiretroviral therapy in Africa, longitudinal health information systems are frail and, therefore, data about long-term survival is often inaccurate or unknown to HIV programmes. The ‘Better Information for Health in Zambia’ (BetterInfo) Study – a regional sampling-based survey to assess retention and mortality in HIV programmes in Zambia – found both retention and mortality to be higher than prevailing estimates from national surveillance systems. We sought to understand how Zambian health decision-makers at different health system levels would respond to these new data, with a view to informing research translation. Methods We interviewed 25 purposefully sampled health decision-makers from community, facility, district, provincial and national levels. During the interviews, we shared retention and mortality estimates from both routine programme surveillance and those generated by the study. Transcripts were analysed for inductive and deductive themes, the latter drawing on Weiss’s framework that policy-makers interpret and apply evidence as ‘warning’, ‘guidance’, ‘reconceptualisation’ or ‘mobilisation of support’. Findings All decision-makers found study findings relevant and important. Decision-makers viewed the underestimates of mortality to be a warning about the veracity and informativeness of routine data systems. Decision-makers felt guided by the findings to improve data monitoring and, acknowledging limitations of routine data, utilised episodic patient tracing to support improved data accuracy. Findings catalysed renewed motivation and mobilisation by national level decision-makers for differentiated models of HIV care to improve patient outcomes and also improved data management systems to better capture patient outcomes. Inductive analysis highlighted a programmatic application data interpretation, in which study findings can influence facility and patient-level decision-making, quality of care and routine data management. Conclusions New epidemiological data on patient outcomes were widely seen as informative and relevant and can potentially catalyse health system action such as using evaluations to supplement electronic medical record data to improve HIV programmes. Formative evidence suggests that targeting research dissemination at different levels of the health system will elicit different responses. Researchers supporting the translation of evidence to action should leverage all relevant levels of the health system to facilitate both policy and programmatic action.
Background: There is no standardized real-world proxy for progression-free survival (PFS), although it is a key treatment response metric in clinical trials. Real-world PFS (rwPFS) has been curated from clinician-documented progression in unstructured electronic health records (EHRs), a time and resource intensive approach, that is not readily accessible in claims or structured EHRs. Alternatively, time to treatment discontinuation (rwTTD) and time to next treatment (rwTTNT) are used as treatment-based scalable proxies of disease progression. We compared clinician-documented rwPFS to rwTTD and rwTTNT. Methods: The study included patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer (A/MBC) who initiated first line treatment with palbociclib plus an aromatase inhibitor (1L) between 2015 and 2019 in US community health systems. Demographics, clinical characteristics, and outcomes were extracted from EHRs. rwPFS was captured through EHR-documented confirmation by two clinicians of disease progression based on imaging and/or pathology results. rwPFS, rwTTD and rwTTNT were defined as the time from 1L initiation until the date of clinician-confirmed progression, 1L discontinuation, or 2L initiation, respectively. Patients were censored at the first of: (1) death, (2) date of last contact, (3) study end date, (4) or at 2L for rwPFS. Results: The study included 241 patients with median age 66 at A/MBC diagnosis, among whom 85% were postmenopausal and 57% were de novo A/MBC. During study follow-up (median 22.4 months), 86 (36%) patients had a clinician-confirmed progression (rwPFS events); 130 (54%) discontinued 1L (rwTTD events), and 96 (40%) initiated 2L (rwTTNT events). With clinician-confirmed progression as the “gold standard”, rwTTD had higher sensitivity (90% vs 71%) but lower specificity (66% vs 77%) than rwTTNT. Patient’s choice, hospice referral, and toxicity were common reasons for treatment discontinuation apart from disease progression. The 12, 24, and 48-month survival estimates were closer between rwPFS (0.78, 0.64, 0.51) and rwTTNT (0.80, 0.63, 0.47), than rwTTD (0.69, 0.51, 0.37). Median rwPFS (39 months, 95% confidence interval [95% CI]: 30-NA) and rwTTNT (32 months, 95% CI: 29-46) were also more alike (log-rank p = 0.90) than median rwPFS and rwTTD (24 months, 95% CI: 18-30; log-rank p=0.02). The correlation between rwPFS and rwTTNT was 0.72 (95% CI: 0.56-0.83), compared to 0.73 (95% CI: 0.57-0.84) between rwPFS and rwTTD. Results were similar in sensitivity analyses where death was part of rwPFS, rwTTNT, and rwTTD events rather than a censoring event. Conclusions: Our results suggest that rwTTNT may be a more adequate at-scale proxy for rwPFS than rwTTD. Studies should assess the generalizability of these findings to other tumor types and treatment settings. Citation Format: Monika A. Izano, Mahder Teka, Colden Johanson, Jeanna Wallenta Law, Ronda Broome, Daniele Morgan, Amy Stone, Mary Tran, Thomas D. Brown, Chenan Zhang. Time to treatment discontinuation and time to next treatment as proxies of real-world progression-free survival in breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4089.
Purpose Using real-world data, interstitial lung disease (ILD) prevalence before and after HER2-directed therapy was estimated. Potential ILD risk factors in patients receiving HER2-directed therapy for metastatic breast cancer (mBC) were evaluated. Methods Adults with HER2-directed therapy for mBC initiated between September 25, 1998, and February 22, 2020 were, included. ILD was defined broadly as one or more of 64 lung conditions. Patients were followed until incident ILD, death, last contact, or study end. Results In total, 533 patients were identified with median age at mBC of 57, 51% had de novo mBC, 43% were ever smokers, 30% had lung metastases, 9% had thoracic radiation, 6% had chronic obstructive pulmonary disease, and 16% had prevalent ILD. ILD cumulative incidence at one year was 9% (95% CI 6%, 12%), with a median follow-up of 23 months. Smoking (HR 2.2, 95% CI 1.1, 4.8) and Black/African-American race (HR 3.4, 95% CI 1.6, 7.5) were significantly associated with ILD; HRs for preexisting lung conditions (HR 1.8, 95% CI 0.9, 3.8) and thoracic radiation (HR 2.3, 95% CI 0.8, 7.1) were not statistically significant. Prevalent ILD was associated with 13-fold greater occurrence of incident ILD. 85% of patients with prevalent or incident ILD were symptomatic. Conclusions This real-world population of patients with mBC had a high prevalence of ILD prior to HER2-directed therapy, reflecting the multifactorial causation of interstitial lung changes. The cumulative incidence of ILD in patients receiving HER2-directed therapy for mBC augments prior reports. Symptomatic presentation suggests an opportunity for early intervention.
e15575 Background: Molecular testing is essential in considering targeted therapies, particularly for the increasing number of metastatic colon cancer (mCC) patients (pts) diagnosed at younger ages who may present with more aggressive disease. This analysis compares demographic and clinical characteristics, and biomarker testing and positivity rates of mCC pts diagnosed at younger versus older ages. Methods: We analyzed 1029 pts with mCC (stage IV at diagnosis) between 01/01/2016 - 12/31/2020 who received care in community health systems in the United States. Pts 18-49 years at mCC diagnosis were considered early onset (EO), and those 50 or older were considered late onset (LO). We compared the distributions of year at diagnosis, gender, race/ethnicity, smoking status, histology, stage at diagnosis, tumor sidedness, KRAS, NRAS, and BRAF testing, and positivity rates between EO and LO mCC pts. Differences in distributions were assessed using chi-square tests. Results: EO pts (n = 148) were more likely to have left-sided tumors than LO pts (n = 881, 55% vs. 36%; p-value < 0.001), and were less likely to be ever smokers (24% vs. 40%; p-value < 0.001); the remaining demographic and clinical characteristics were similar between the two groups. Testing was significantly more common among EO than LO pts for KRAS (71% vs 48%), NRAS (39% vs 29%), and BRAF (41% vs 31%) (Table). Annual NRAS and BRAF testing rates increased between 2016 - 2020 for both groups: NRAS rates increased from 13% to 41%, and 5% to 37%, for EO and LO pts, respectively; BRAF rates increased from 13% to 41%, and 5% to 40%, for EO and LO pts, respectively. KRAS testing rates held at a consistent rate over time for EO pts, and increased over time among LO mCC pts (35% - 52%). The positivity rates for KRAS, NRAS and BRAF mutations were similar among tested pts in both groups. Conclusions: In this real world analysis, pts with EO mCC were more likely to have left sided primary cancers, and less likely to have a smoking history. Of note, BRAF testing showed a marked increase over time among all mCC pts. EO pts were more likely to receive KRAS, NRAS and BRAF testing. Further understanding of the correlates of EO mCC, biomarker testing practices, and subsequent treatment decisions is critical to improving pt outcomes.[Table: see text]
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.