The use of dietary supplements is common in the general population and even more prevalent among cancer survivors. The World Cancer Research Fund/American Institute for Cancer Research specifies that dietary supplements should not be used for cancer prevention. Several dietary supplements have potential pharmacokinetic and pharmacodynamic interactions that may change their clinical efficacy or potentiate adverse effects of the adjuvant endocrine therapy prescribed for breast cancer treatment. This analysis examined the prevalence of self-reported dietary supplement use and the potential interactions with tamoxifen and aromatase inhibitors (AIs) among breast cancer survivors enrolled in three randomized controlled trials of lifestyle interventions conducted between 2010 and 2017. The potential interactions with tamoxifen and AIs were identified using the Natural Medicine Database. Among 475 breast cancer survivors (2.9 (mean) or 2.5 (standard deviation) years from diagnosis), 393 (83%) reported using dietary supplements. A total of 108 different types of dietary supplements were reported and 36 potential adverse interactions with tamoxifen or AIs were identified. Among the 353 women taking tamoxifen or AIs, 38% were taking dietary supplements with a potential risk of interactions. We observed a high prevalence of dietary supplement use among breast cancer survivors and the potential for adverse interactions between the prescribed endocrine therapy and dietary supplements was common.
Abstract Background: Several neoadjuvant and adjuvant treatment options exist for patients with HER2-positive (HER2+) stage II-III breast cancer. Recent results of the KATHERINE trial (NCT01772472) showed that adjuvant T-DM1 can reduce distant recurrence risk in patients without pathologic complete response (pCR) after neoadjuvant chemotherapy. However, pCR rates can range between 20-80% depending on treatment regimen and subtype. Given the high cost of T-DM1 and other HER2-targeted agents, understanding the relationship between the costs and health consequences of various neoadjuvant-adjuvant treatment combinations is needed. Our goal is to identify the treatment strategy that leads to the highest health benefit (i.e., lowest distant recurrence risk) at the least costs. Methods: We developed a decision-analytic Markov model to simulate clinical practice in a cohort of women aged ≥49 with HER2+ breast cancer similar to the KATHERINE trial population. We considered 4 neoadjuvant regimens: HP: trastuzumab (H) and pertuzumab (P) doublet; THP: paclitaxel (T), H and P triplet; ddAC/THP: dose dense anthracycline/cyclophosphamide (ddAC) followed by T, H, P; TCHP: docetaxel (T), carboplatin (C), H, and P, and 4 adjuvant treatments for patients with residual disease including: H; T-DM1; ddAC/THP followed by T-DM1; and ddAC followed by T-DM1. We combined these neoadjuvant and adjuvant treatment options to mimic four clinically plausible treatment de-escalation strategies and examined their cost effectiveness. All patients with pCR after any neoadjuvant treatment received adjuvant H. Strategies for residual disease: 1: neoadjuvant-ddAC/THP+adjuvant-H; 2: neoadjuvant-ddAC/THP+adjuvant-T-DM1; 3: neoadjuvant-THP+adjuvant-ddAC followed by T-DM1; 4: neoadjuvant-HP+adjuvant-ddAC/THP followed by T-DM1; 5: neoadjuvant-TCHP+adjuvant-T-DM1. We informed the effectiveness, cost and utility parameters from the KATHERINE trial, McKesson data, and published literature. We estimated costs and quality-adjusted life years (QALYs) over a lifetime for each strategy, and an incremental cost-effectiveness ratio (ICER), from a healthcare payer perspective and addressed the uncertainty with a probabilistic sensitivity analysis (PSA). Results: The mean per-patient costs varied between $274,550 (Strategy 3) and $354,652 (Strategy 4) and the mean per-patient QALYs varied between 9.44 (Strategy 1) and 10.56 (Strategy 3). When considering the five treatment strategies, Strategy 3 yielded a substantial gain in QALYs at decreased costs, representing the dominating strategy. The decision-analytic model identified Strategies 1, 2, 4 and 5 to be cost-ineffective due to their lower health effects and higher costs (i.e., dominated strategies). PSA indicated Strategy 3 to have the highest probability of cost-effectiveness and expected net benefit across a wide range of willingness-to-pay thresholds ($0-250,000). These findings persisted when changing a number of assumptions, including increasing starting age and varying pCR rates and distant recurrence probability after an initial local recurrence. Conclusions: Our study indicates that neoadjuvant trastuzumab+paclitaxel+pertuzumab followed by adjuvant trastuzumab for patients with pCR (around 46% of patients) and by adjuvant ddAC and T-DM1 for those with residual disease is the most cost-effective treatment strategy for women with HER2+, stage II-III breast cancer. StrategyCostsQALYsICERStrategy 3 Neoadjuvant T, H, P Adjuvant ddAC+T-DM1 for RD; H for pCR$274,55010.56-Strategy 1 Neoadjuvant T, H, P, ddAC Adjuvant H for RD; H for pCR$278,8829.44DominatedStrategy 2 Neoadjuvant T, H, P, ddAC Adjuvant T-DM1 for RD; H for pCR$293,98210.04DominatedStrategy 5 Neoadjuvant T, C, H, P Adjuvant T-DM1 for RD; H for pCR$316,26610.46DominatedStrategy 4 Neoadjuvant H, P Adjuvant T, H, P, ddAC+T-DM1 for RD; H for pCR$354,65210.15Dominated* “Dominated” strategy leads to fewer QALYs at higher costs than the next least costly treatment alternative. Citation Format: Natalia R. Kunst, Shi-Yi Wang, Annette Hood, Sarah Mougalian, Michael P. DiGiovanna, Kerin Adelson, Lajos Pusztai. Cost-effectiveness of different neoadjuvant followed by adjuvant treatment combination strategies for women with HER2-positive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD10-05.
585 Background: Ado-trastuzumab emtansine (T-DM1) is currently approved for patients with trastuzumab-resistant HER2-positive metastatic breast cancer (MBC). However, there is no data on the activity of T-DM1 in patients who received prior pertuzumab, now included as standard first line therapy. The goal of this study was to assess the efficacy of T-DM1 in routine clinical practice in a contemporary patient population that received prior trastuzumab and pertuzumab. Methods: We identified all patients with HER2-positive MBC who received T-DM1 after trastuzumab and pertuzumab between March 1, 2013 and July 15, 2015 through electronic pharmacy records and departmental databases at 3 institutions, MD Anderson Cancer Center, Smilow Cancer Hospital at Yale and The James Cancer Hospital at the Ohio State University. We reviewed the medical records of each case to confirm treatment sequencing and outcome. Results: Eighty-two patients were identified and 78 were available for outcome analysis; 32% received T-DM1 as 1st/2nd line therapy and 48% received it as > 4th line treatment. Response rate was 17.9% (95% CI, 9.4-26.4%). Median duration on therapy was 4.0 months (95% CI, 2.7-5.1, range: 0-22.5). Clinical benefit rate (CBR), defined as complete or partial response or treatment duration > 6 months, was 37.2% (95% CI, 26.5-47.9%). T-DM1 was discontinued for disease progression in 84% of patients and for toxicity in 10%. Conclusions: Tumor response rates were lower than prior reports in trastuzumab-resistant HER2-positive MBC, but one third of patients received T-DM1 for > 6 months which suggests clinically relevant benefit to T-DM1 in patients who received prior pertuzumab. Physician designated tumor response rate (ORR). Characteristic No. of Patients % 95% CI All Patients 78 ORR 14 17.9 9.4 to 26.4 Hormone Receptor Status ER and/or PR-positive 49 ORR 10 20.4 9.1 to 31.7 ER and PR-negative 29 ORR 4 13.8 1.3 to 26.4 T-DM1 as 2nd Line Therapy 26 ORR 6 23.1 6.9 to 39.3 T-DM1 as > 2nd Line Therapy 52 ORR 8 15.4 5.6 to 25.2 Recurrence Free Interval De Novo Metastatic Disease 33 ORR 7 21.2 7.3 to 35.2 Met. Recurrence < 1 year after diagnosis 14 ORR 3 21.4 0 to 42.9 Met. Recurrence > 1 year after diagnosis 31 ORR 4 12.9 1.1 to 24.7
"BPI23-012: Real-World Frequency of ECHO Monitoring and Incidence of Anti-HER2 Therapy Related Cardiac Events in HER2+ Breast Cancer Patients" published on 31 Mar 2023 by National Comprehensive Cancer Network.
Abstract Background: Dietary supplements (DS), defined as herbal preparations, vitamins and minerals (DSHEA Act 1994), are used by 70% of cancer survivors. The World Cancer Research Fund/American Institute for Cancer Research 2018 Cancer Prevention Recommendations specify not to use DS to protect against cancer. There is some evidence that DS are linked to harmful outcomes, including increased mortality and breast cancer recurrence. DS have potential pharmacokinetic interactions via cytochrome P450 enzyme and pharmacodynamic interactions via estrogenic or hepatotoxic activity, which may increase or reduce clinical efficacy or potentiate adverse effects of Tamoxifen and Aromatase Inhibitors (AIs). This analysis examines baseline usage of DS and potential interactions with Tamoxifen and AIs among breast cancer survivors enrolled in the Lifestyle, Exercise, and Nutrition (LEAN) study, a randomized healthy eating and exercise lifestyle intervention. Methods: We examined the use of DS in 151 breast cancer survivors enrolled in the LEAN Study. Women with a body mass index (BMI) ≥ 25 kg/m 2 were randomly assigned to a 6-month healthy eating and exercise lifestyle intervention (n=93) or to usual care (n=58). At baseline and 6 months, we asked participants to self-report regular DS use, defined as at least 3 times a week for at least one month. The intervention group received evaluation and counseling of DS use by a Registered Dietitian (RD) with a Certified Specialty in Oncology Nutrition (CSO). Potential interactions of moderate and major ratings between DS with Tamoxifen and AIs (Letrozole, Exemestane and Anastrozole) were identified through the Natural Medicines Database by both a pharmacist specializing in oncology and a RD, CSO. Results: Out of 151 women, at baseline 120 (80%) reported using DS. Fifty-four different formulations were enumerated. The majority of women (72, 60%) were taking ≥ 3 formulations. One quarter of women (29, 24%) were taking ≥ 5 formulations (range = 1 - 20). Of the 54 formulations, 33% had potential interactions with Tamoxifen and/or AIs according to the Natural Medicines Database. Total interactions by medication were: 18 Tamoxifen, 14 Letrozole, 14 Exemestane, 9 Anastrozole. The majority of these interactions (87%) were associated with herbal preparations. Conclusions: Our findings are indicative of the high prevalence of DS use among breast cancer survivors and the potential risk of interactions with prescribed hormonal therapy. More research is needed to test if counseling from a RD, CSO can reduce DS use and ultimately lead to better outcomes due to fewer interactions with breast cancer treatments. Citation Format: ThaiHien Nguyen, Maura Harrigan, Courtney Mcgowan, Annette Hood, Fangyong Li, Brenda Cartmel, Leah Ferrucci, Melinda L Irwin, Tara Sanft. Dietary supplement use in a healthy eating and exercise lifestyle intervention in breast cancer survivors: The lifestyle exercise and nutrition (LEAN) study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-09.
e18834 Background: Substantial advances in treatment of metastatic breast cancer (mBC) have led to changes in clinical practice and treatment costs in the United States in the past decade. We aimed to identify treatment patterns in mBC patients by subgroup and year after mBC diagnosis and associated costs from payer and societal perspectives. Methods: This study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database (1/2011-5/2021). We excluded cases that were male, had < 6 months of follow up, no treatment data, no structured data within 90 days of diagnosis, participated in clinical trials, had non-breast invasive cancers, received therapies not used in mBC, had no data on human epidermal growth factor (HER2) and hormone receptor (HR) status. We classified patients into four subgroups: HER2-HR+, HER2+HR+, HER2+HR-, and Triple Negative (TNBC). We calculated anti-cancer and supportive drug costs at the patient level and mean costs by year after diagnosis for each subgroup. We used average wholesale prices (AWP, from McKesson Corporation) for payer perspective and Medicare prices (part B payment limit data, Part D Drug Spending Dashboard) for societal perspective. We estimated costs up to year 5 after diagnosis of mBC (< 8% received treatment after year 5). Results: 15,215 patients met the criteria (64.41% non-Hispanic White, 66.85% HER2-HR+, 18.30% HER2+HR+, 5.27% HER2+HR-, 9.58% TNBC). AWP and Medicare cost estimates by year after diagnosis and subgroup are shown in Table. 334,812 for HER2+HR+, $284,609 for HER2+HR-, $104,774 for HER2-HR+, and $54,355 for the TNBC. We observed an increase in annual costs between years 2011-2021 in most subgroups. This increase was most substantial for HER2-HR+ patients. From 2011 to 2019 (most recent complete year 1 data is for patients diagnosed in 2019), annual Medicare treatment costs in year 1 increased from $12,986 to $80,563 for HER2-HR+, $99,997 to $156,712 for HER2+HR+, and $31,397 to $53,775 for TNBC. There was no increase in costs of treating HER2+HR- in year 1, but an increase in year 2 (from $90,427 to $129,690 between 2011-2019). Conclusions: mBC treatment costs vary significantly by receptor subtype and years after diagnosis. Annual costs increased over time. Costs were greatest for HER2+ and lowest for TNBC.[Table: see text]
Background: Real-world data regarding the use of poly (ADP-ribose) polymerase (PARP) inhibitors in recurrent ovarian cancer patients with non-BRCA homologous recombination (HR) mutations or somatic BRCA mutations are lacking. Objective: The purpose of our study is to evaluate the response rate, duration of treatment, time to progression (TTP), and toxicities of olaparib, niraparib, and rucaparib in somatic BRCAm and non-BRCA HR-mutated patients. Methods: This was a retrospective study using the electronic medical record to identify patients across our health system who were initiated on a PARP inhibitor for ovarian cancer between December 2014 and December 2019. Patients were screened for the presence of a somatic BRCA1/2 mutation or a mutation in non-BRCA HR genes. Data were collected via chart review. Results: For the efficacy analysis, 8 patients had somatic BRCA mutations and 12 patients had HR mutations. The overall response rate (ORR) was 50% for BRCA-mutated (BRCAm) patients and 9.1% for non-BRCA HR-mutated (non-BRCA HRm) patients. 72.7% of patients with non-BRCA HR mutations had stable disease. The duration of therapy ranged from 2 to 66 months. The median TTP was 9.5 months. Overall, 66.7% of patients in the entire cohort started on a reduced dose of PARP inhibitor. Dose reductions due to AEs were observed in 52.4% of patients, while AEs requiring treatment interruption occurred in 61.9%. Conclusion and Relevance: We found that PARP inhibitors provided stable disease in a high proportion of recurrent ovarian cancer patients who had pathogenic HR mutations, with toxicities comparable to major trials. Patients with non-BRCA HR and somatic BRCA mutations could benefit from PARP inhibitors.
Advances in treatment of metastatic breast cancer (MBC) led to changes in clinical practice and treatment costs in the US over the past decade. There is limited information on current MBC treatment sequences and associated costs by MBC subtype in the US.To identify treatment patterns by MBC subtype and associated anticancer and supportive drug costs from health care sector and Medicare perspectives.This economic evaluation analyzed data of patients with MBC obtained from the nationwide Flatiron Health database, an electronic health record-derived, deidentified database with data from community and academic practices across the US from 2011 to 2021. Participants included women aged at least 18 years diagnosed with MBC, who had at least 6 months of follow-up data, known hormone receptor (HR) and human epidermal growth factor receptor 2 (ERBB2) receptor status, and at least 1 documented line of therapy. Patients with documented receipt of clinical study drugs were excluded. Data were analyzed from June 2021 to May 2022.Outcomes of interest were frequency of different drug regimens received as a line of therapy by subtype for the first 5 lines and mean medical costs of documented anticancer treatment and supportive care drugs per patient by MBC subtype and years since metastatic diagnosis, indexed to 2021 US dollars.Among 15 215 patients (10 171 patients [66.85%] with HR-positive and ERBB2-negative MBC; 2785 patients [18.30%] with HR-positive and ERBB2-positive MBC; 802 patients [5.27%] with HR-negative and ERBB2-positive MBC; 1457 patients [9.58%] with triple-negative breast cancer [TNBC]) who met eligibility criteria, 1777 (11.68%) were African American, 363 (2.39%) were Asian, and 9800 (64.41%) were White; the median (range) age was 64 (21-84) years. The mean total per-patient treatment and supportive care drug cost using publicly available Medicare prices was $334 812 for patients with HR-positive and ERBB2-positive MBC, $284 609 for patients with HR-negative and ERBB2-positive MBC, $104 774 for patients with HR-positive and ERBB2-negative MBC, and $54 355 for patients with TNBC. From 2011 to 2019 (most recent complete year 1 data are for patients diagnosed in 2019), annual costs in year 1 increased from $12 986 to $80 563 for ERBB2-negative and HR-positive MBC, $99 997 to $156 712 for ERBB2-positive and HR-positive MBC, and $31 397 to $53 775 for TNBC.This economic evaluation found that drug costs related to MBC treatment increased between 2011 and 2021 and differed by tumor subtype. These findings suggest the growing financial burden of MBC treatment in the US and highlights the importance of performing more accurate cost-effectiveness analysis of novel adjuvant therapies that aim to reduce metastatic recurrence rates for early-stage breast cancer.
Purpose To evaluate and compare the rate of hypersensitivity reactions between two low-dose steroid pre-medication regimens for paclitaxel-based treatments. Methods This was a single-center, retrospective, descriptive study, comparing the incidence of hypersensitivity reactions in two different dexamethasone pre-medication regimens that took place between July 2013 to December 2014. Patients who were paclitaxel-naïve with a diagnosis of breast or gynecological cancers were included. Patients in the early termination protocol were pre-medicated with a standard pre-medication regimen and if tolerated with no hypersensitivity reaction occurrence, all pre-medications were discontinued after the first two infusions. Patients in the low-dose steroid continuation protocol were pre-medicated with lower doses of dexamethasone, and if the infusion was tolerated with no hypersensitivity reaction, dexamethasone doses were further reduced after the first two infusions. Results A total of 120 patients were included for data analysis. The hypersensitivity reaction rate in the early termination protocol group was 7% (4 out of 60 patients). The hypersensitivity reaction rate in the low-dose continuation protocol group was 5% (3 out of 60 patients). All hypersensitivity reactions occurred during the first infusion, with no hypersensitivity reactions occurring once the dexamethasone pre-medications were discontinued or dose-reduced. All of the patients who experienced a hypersensitivity reaction were successfully re-challenged with paclitaxel and were able to continue their therapy uninterrupted. Conclusion Discontinuing dexamethasone pre-medication altogether after two uneventful infusions or decreasing the dose of dexamethasone paclitaxel pre-medication are both safe alternatives to high-dose steroid pre-medications recommended in product labeling.
Purpose Ado-trastuzumab emtansine (T-DM1) is currently approved for treatment in patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (MBC) who previously received trastuzumab and a taxane. However, there are no data on the activity of T-DM1 in patients who received prior pertuzumab, which is now included as standard first-line therapy. The goal of this study was to assess the efficacy of T-DM1 in routine clinical practice in a contemporary patient population that received both prior trastuzumab and pertuzumab. Patients and Methods We identified all patients with HER2-positive MBC who received T-DM1 after trastuzumab and pertuzumab between March 1, 2013, and July 15, 2015, via electronic pharmacy records and departmental databases at three institutions: MD Anderson Cancer Center, Smilow Cancer Hospital at Yale, and The James Cancer Hospital at the Ohio State University. We reviewed medical records of each case to confirm treatment sequencing and outcome. Results Of patients, 82 were identified and 78 were available for outcome analysis; 32% received T-DM1 as first- and second-line line therapy, and 48% received it as fourth-line treatment or later. Rate of prolonged duration on therapy, defined as duration on therapy ≥ 6 months, was 30.8% (95% CI, 20.6% to 41.1%), and tumor response rate was 17.9% (95% CI, 9.4% to 26.4%). Median duration on therapy was 4.0 months (95% CI, 2.7 to 5.1; range, 0 to 22.5 months). T-DM1 was discontinued for disease progression in 84% of patients and for toxicity in 10%. Conclusion Tumor response rates were lower than in prior reports of trastuzumab-resistant, HER2-positive MBC, but one third of patients received therapy with T-DM1 for ≥ 6 months, which suggests a clinically relevant benefit in patients who received prior pertuzumab.
