ABSTRACT
Introduction: We performed matched case-control studies utilizing cohorts of postmenopausal women with ER+ breast cancer receiving adjuvant aromatase inhibitors (AI) on MA.27 [anastrozole, exemestane] or PreFace [letrozole] to assess the association between estrogen suppression after 6 months of treatment and an early breast cancer (EBC) event within 5 years of AI initiation (Clin Cancer Res 2020;26:2986-98). We found a significant 3.0-fold increase in risk of an EBC event for those taking anastrozole with levels of estrone (E1) >=1.3 pg/mL and estradiol (E2) >=0.5 pg/mL, but not for exemestane or letrozole. Given these findings we designed a prospective pharmacodynamic (PD) study to evaluate the impact of anastrozole (1 mg/day: ANA1) on E1 and E2 levels, and among those with inadequate estrogen suppression (IES: E1 >=1.3 pg/mL and E2 >=0.5 pg/mL), to evaluate the safety and PD efficacy of high-dose anastrozole (10 mg/day: ANA10), which has been found to be safe in prior clinical trials (Cancer 1998;83:1142-52). Method(s): Post-menopausal women with stage I-III, ER >=1% positive/HER2-negative breast cancer who were candidates for anastrozole were eligible after completion of locoregional therapy and chemotherapy, as clinically indicated. Women who were pre-menopausal at diagnosis were not eligible. All patients received 8-10 weeks of ANA1, after which those with adequate estrogen suppression (AES: E1< 1.3 pg/mL or E2< 0.5 pg/mL) came off study. Those with IES went on to receive ANA10 for 8-10 weeks, followed by letrozole (2.5 mg/day: LET) for 8-10 weeks. All patients were managed at their treating oncologist's discretion following study discontinuation. E1 and E2 blood levels were measured pre-treatment and after completion of each treatment cycle by a CLIA-approved liquid chromatography with tandem mass spectrometry in the Immunochemical Core Laboratory at Mayo Clinic. With a sample size of 29 patients with IES after ANA1, a one-sided binomial test of proportions with a significance level of 0.05 will have an 87% chance of rejecting the proportion with AES after ANA10 is at most 25% (Ho) when the true proportion is at least 50%. Specifically, the null hypothesis is rejected if the number of women with AES after ANA10 is 12 or more. Data lock was July 6, 2022. Result(s): Of the 161 women enrolled from April 2020 through May 2022, 3 withdrew consent prior to start of ANA1 and 2 were ineligible;thus, 156 women comprised the study cohort. Median patient age was 64 years (range 44-86), 10% of patients were of Hispanic ethnicity and/or non-white race, and 15% received chemotherapy. Six patients remain on ANA1, and 10 discontinued ANA1 due to refusal (7), adverse event (AE) (2), or COVID-19 (1). Forty-one of the remaining 140 patients (29.3% 95%CI: 21.9- 37.6%) had IES with ANA1. Nine of these 41 patients did not go on to ANA10 due to refusal (6) or AE (3). Of the 32 patients who started ANA10, 8 remain on treatment, 5 discontinued due to refusal (3) or AE (1-grade 2 urinary tract infection;1-grade 1 palpitations), and 19 had a blood draw 45 days or more after starting ANA10. No grade 3-5 AEs or grade 2 hot flashes or arthralgias were reported. Of these 19 patients, 14 achieved AES with ANA10 (73.7% 95%CI: 48.8-90.9%). All 19 patients switched to LET of which 3 remain on treatment, 1 is missing E1/E2 data, and 15 had a blood draw 45 days or more after starting LET. Of these 15 patients, 10 maintained AES, 2 acquired AES with LET, and 3 no longer had AES. Anastrozole and letrozole drug levels will be reported at the meeting. Conclusion(s): Approximately 29% of postmenopausal women with ER+/HER2- BC receiving adjuvant anastrozole 1 mg/daily had IES. A majority of these patients achieved AES with dose escalation to ANA10 without tolerability issues. E1 and E2 levels are logical biomarkers given the mechanism of action of anastrozole, and further study utilizing them to determine the optimal dose of anastrozole for a given patient should be performed.
ABSTRACT
Background: We previously demonstrated that utilization of a Remote Patient Monitoring (RPM) program - characterized by the use of in-home technology for symptom and vital signs assessments with a centralized care team responding to alerts - is associated with a significant reduction in 30-day hospitalization rate among cancer patients with COVID-19. We have subsequently performed a 90-day comparative cost-of-care analysis in this prospectively enrolled, validated cohort of 71 patients who received RPM and 116 patients who received usual care without RPM. Method(s): Primary outcomes included 90-day all-cause costs (categorized as hospital and outpatient costs) following the index date (date of COVID-19 diagnosis). Differences in patient characteristics and baseline costs (incurred 90 days prior to index date) were determined using Standardized Differences and controlled for using Inverse Probability Weighting (IPW). IPW balancing was based on baseline covariates known to be associated with poorer COVID-19 outcomes, as previously described. Association of costs with RPM was examined by generalized linear modeling while adjusting for relevant variables. Outcomes are reported as the average treatment effect on the treated (ATET). Result(s): Differences in patient characteristics and baseline costs were well-balanced following IPW modeling. The index ATET was found to be comparable among patients receiving RPM and usual care on the date of COVID-19 diagnosis -$89.75 (95% CI: -$144.33 to $323.84;p = 0.452). However, patients receiving RPM experienced a 90-day ATET of -$6,994 (95% CI: -$14,635 to $646;p = 0.073) when compared with patients receiving usual care. Conclusion(s): There was a trend towards decreased 90-day all-cause costs for cancer patients with COVID-19 who utilized the RPM program as compared with usual care. Larger studies are needed to understand the true cost (and cost savings) associated with this innovative model of care delivery which can be leveraged for cancer care beyond COVID-19.
ABSTRACT
Background: In response to the COVID-19 pandemic, many cancer practices adopted telehealth, including telephone and video appointments. Following a period of initial expansion that began in March 2020, sustained telehealth integration has emerged across the Mayo Clinic Cancer Practice (MCCP) in 2021. The primary objective of this study was to identify factors associated with utilization of telehealth appointments. Methods: A cross-sectional, multi-site, retrospective analysis was conducted across MCCP - a multisite, multiregional cancer practice with tertiary referral campuses in Minnesota, Florida, and Arizona, as well as rural, community-based hospitals and clinics throughout the Upper Midwest. Multivariable models were used to examine the association of patient- and provider-level variables with telehealth utilization. Results: Outpatient appointments conducted in July - August 2019 (n = 32,932) were compared with those from 2020 (n = 33,662) and 2021 (n = 35,486). The rate of telehealth appointment utilization increased from <0.01% in 2019 to 11.0% in 2020 and 14.0% in 2021. The strongest provider-level predictor of telehealth utilization was female physician provider type (OR 1.06, 95% CI 1.01 to 1.11;P = 0.0297), a trend consistently observed across career stages, practice locations and settings in 2020 and 2021. Additionally, while the rate of telehealth utilization was not significantly different at referral and community-based campuses in 2020, providers at referral campuses were significantly more likely to utilize telehealth than community-based campuses in 2021 (OR 1.1, 95% CI 1.01 to 1.12;P = 0.0289). Regarding patient-level factors, rural residence (defined by Rural-Urban Commuting Area codes), which accounted for 44.2% of the patient population, was significantly associated with lower telehealth utilization as compared to patients with urban residences, particularly for video appointments (OR 1.04, 95% CI 1.02 to 1.07;P < 0.0001). Notably, the disparity in telehealth utilization between rural and urban populations was found to be less pronounced in 2021 as compared to 2020. Conclusions: Multivariable analysis across a multi-site, multi-regional cancer practice identified several factors associated with increased telehealth utilization. These included female physician provider type, referral-based campuses, and patients residing in urban settings. A detailed understanding of the factors that influence telehealth utilization - a method of care delivery which represents a “new normal” across many cancer practices - will be essential to enable continued equitable access to high-quality, high-impact, patient-centered cancer care.
ABSTRACT
Background: Patients with cancer and COVID-19 are at risk for poor clinical outcomes. An established multi-site remote patient monitoring (RPM) service was rapidly adapted to support a novel, interdisciplinary COVID-19 program for outpatient management of patients at high-risk for severe illness. The goal of this study was to assess the impact of the RPM program on clinical outcomes and acute care utilization in cancer patients diagnosed with COVID-19. Methods: This is a crosssectional analysis following a multi-site prospective observational study performed at Mayo Clinic Cancer Center (MCCC). All adult patients with active cancer - defined as currently receiving cancer-directed therapy or in recent remission on active surveillance - and PCR-confirmed SARS-CoV-2 infection between March 18 and July 31, 2020 were included. RPM was comprised of in-home technology to assess symptoms and physiologic data with centralized nurse and physician oversight. Results: During the study timeframe 224 cancer patients were diagnosed with COVID-19 at MCCC. Initial management included urgent hospitalization (within 48 hours of diagnosis) in 34 patients (15%). Of the remaining 190 patients (85%) initially managed in the outpatient setting, those who did not receive RPM were significantly more likely to experience hospitalization than those receiving RPM (OR 3.6, 95% CI 1.036 to 12.01, P = 0.044). Following balancing of patient characteristics by inverse propensity weighting, rates of hospital admission for RPM and non-RPM patients were 3.1% and 11% respectively, implying that RPM was associated with an 8% reduction in hospital admission rate (-0.077;95% CI: -0.315 to -0.019, P = 0.009). Use of RPM was also associated with lower rates of prolonged hospitalization, ICU admission, and mortality, though these trends did not reach statistical significance. Conclusions: In the midst of a global pandemic associated with inpatient bed, ventilator, and PPE shortages, the RPM program provided an effective strategy for outpatient clinical management and was associated with decreased rates of hospitalization, ICU admission, and mortality in cancer patients with COVID-19. This care model enabled simultaneous opportunity to mitigate the increased risks of exposure, transmission, and resource utilization associated with conventional care.