Cost-Effectiveness of Neoadjuvant-Adjuvant Treatment Strategies for Women With ERBB2 (HER2)-Positive Breast Cancer

IMPORTANCE: The neoadjuvant treatment options for ERBB2-positive (also known as HER2-positive) breast cancer are associated with different rates of pathologic complete response (pCR). The KATHERINE trial showed that adjuvant trastuzumab emtansine (T-DM1) can reduce recurrence in patients with residual disease compared with patients treated with trastuzumab; however, T-DM1 and other ERBB2-targeted agents are costly, and understanding the costs and health consequences of various combinations of neoadjuvant followed by adjuvant treatments in the United States is needed. OBJECTIVE: To examine the costs and disease outcomes associated with selection of various neoadjuvant followed by adjuvant treatment strategies for patients with ERBB2-positive breast cancer. DESIGN, SETTING, AND PARTICIPANTS: In this economic evaluation, a decision-analytic model was developed to evaluate various neoadjuvant followed by adjuvant treatment strategies for women with ERBB2-positive breast cancer from a health care payer perspective in the United States. The model was informed by the KATHERINE trial, other clinical trials with different regimens from the KATHERINE trial, the Flatiron Health Database, McKesson Corporation data, and other evidence in the published literature. Starting trial median age for KATHERINE patients was 49 years (range, 24-79 years in T-DM1 arm and 23-80 years in trastuzumab arm). The model simulated patients receiving 5 different neoadjuvant followed by adjuvant treatment strategies. Data analyses were performed from March 2019 to August 2020. EXPOSURE: There were 4 neoadjuvant regimens: (1) HP: trastuzumab (H) plus pertuzumab (P), (2) THP: paclitaxel (T) plus H plus P, (3) DDAC-THP: dose-dense anthracycline/cyclophosphamide (DDAC) plus THP, (4) TCHP: docetaxel (T) plus carboplatin (C) plus HP. All patients with pCR, regardless of neoadjuvant regimen, received adjuvant H. Patients with residual disease received different adjuvant therapies depending on the neoadjuvant regimen according to the 5 following strategies: (1) neoadjuvant DDAC-THP followed by adjuvant H, (2) neoadjuvant DDAC-THP followed by adjuvant T-DM1, (3) neoadjuvant THP followed by adjuvant DDAC plus T-DM1, (4) neoadjuvant HP followed by adjuvant DDAC/THP plus T-DM1, or (5) neoadjuvant TCHP followed by adjuvant T-DM1. MAIN OUTCOMES AND MEASURES: Lifetime costs in 2020 US dollars and quality-adjusted life-years (QALYs) were estimated for each treatment strategy, and incremental cost-effectiveness ratios were estimated. A strategy was classified as dominated if it was associated with fewer QALYs at higher costs than the alternative. RESULTS: In the base-case analysis, costs ranged from $415 833 (strategy 3) to$518 859 (strategy 4), and QALYs ranged from 9.67 (strategy 1) to 10.73 (strategy 3). Strategy 3 was associated with the highest health benefits (10.73 QALYs) and lowest costs ($415 833) and dominated all other strategies. Probabilistic analysis confirmed that this strategy had the highest probability of cost-effectiveness (>70$0-200,000/QALY) and was associated with the highest net benefit. CONCLUSIONS AND RELEVANCE: These results suggest that neoadjuvant THP followed by adjuvant H for patients with pCR or followed by adjuvant DDAC plus T-DM1 for patients with residual disease was associated with the highest health benefits and lowest costs for women with ERBB2-positive breast cancer compared with other treatment strategies considered

Breast Cancer Survivorship Care Variations Between Adjuvant Chemotherapy Regimens.

BackgroundTreatment-related toxicity can vary substantially between chemotherapy regimens. In this study we evaluated the frequency of outpatient office visits among a cohort of early stage breast cancer survivors after completion of 4 different adjuvant chemotherapy regimens to better understand how differences in toxicities between regimens might affect health care use.Materials and methodsWe analyzed administrative claims data from a US commercial insurance database (OptumLabs) to identify women who received adjuvant doxorubicin/cyclophosphamide (AC), AC followed or preceded by docetaxel or paclitaxel (AC-T), AC concurrent with docetaxel or paclitaxel (TAC), or docetaxel/cyclophosphamide (TC) between 2008 and 2014. We compared mean numbers of visits per patient (adjusted for age, race/ethnicity, region, year, surgery type, radiation, chronic conditions, and previous hospitalizations) across the different regimens (TC = reference) for 12 months, starting 4 months after the end of chemotherapy.ResultsIn 6247 eligible patients, the mean adjusted number of outpatient visits per patient was significantly higher in patients who received AC-T (8.1) or TAC (7.3) than TC (6.5) or AC (6.0; P < .001 for comparisons of AC-T and TAC with TC), primarily because of differences in Medical Oncology visits. Approximately 40% did not see a primary care provider at all during this time frame.ConclusionsAC-T and TAC are associated with more subsequent outpatient visits than TC. Visits to primary care providers are infrequent during the year after completion of chemotherapy

Breast Cancer Survivorship Care Variations Between Adjuvant Chemotherapy Regimens

BackgroundTreatment-related toxicity can vary substantially between chemotherapy regimens. In this study we evaluated the frequency of outpatient office visits among a cohort of early stage breast cancer survivors after completion of 4 different adjuvant chemotherapy regimens to better understand how differences in toxicities between regimens might affect health care use.Materials and methodsWe analyzed administrative claims data from a US commercial insurance database (OptumLabs) to identify women who received adjuvant doxorubicin/cyclophosphamide (AC), AC followed or preceded by docetaxel or paclitaxel (AC-T), AC concurrent with docetaxel or paclitaxel (TAC), or docetaxel/cyclophosphamide (TC) between 2008 and 2014. We compared mean numbers of visits per patient (adjusted for age, race/ethnicity, region, year, surgery type, radiation, chronic conditions, and previous hospitalizations) across the different regimens (TC = reference) for 12 months, starting 4 months after the end of chemotherapy.ResultsIn 6247 eligible patients, the mean adjusted number of outpatient visits per patient was significantly higher in patients who received AC-T (8.1) or TAC (7.3) than TC (6.5) or AC (6.0; P < .001 for comparisons of AC-T and TAC with TC), primarily because of differences in Medical Oncology visits. Approximately 40% did not see a primary care provider at all during this time frame.ConclusionsAC-T and TAC are associated with more subsequent outpatient visits than TC. Visits to primary care providers are infrequent during the year after completion of chemotherapy

Risk of myeloid neoplasms after radiotherapy among older women with localized breast cancer: A population-based study

<div><p>Background</p><p>There are inconsistent and limited data regarding the risk of myeloid neoplasms (MN) among breast cancer survivors who received radiotherapy (RT) in the absence of chemotherapy. Concern about subsequent MN might influence the decision to use adjuvant RT for women with localized disease. As patients with therapy-related MN have generally poor outcomes, the presumption of subsequent MN being therapy-related could affect treatment recommendations.</p><p>Methods</p><p>We used the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database to study older women with in-situ or stage 1–3 breast cancer diagnosed 2001–2009 who received surgery. Chemotherapy and RT were ascertained using Medicare claims, and new MN diagnoses were captured using both SEER registry and Medicare claims. We excluded women who received chemotherapy for initial treatment, and censored at receipt of subsequent chemotherapy. Competing-risk survival analysis was used to assess the association between RT and risk of subsequent MN adjusting for relevant characteristics.</p><p>Results</p><p>Median follow-up for 60,426 eligible patients was 68 months (interquartile range, 46 to 92 months), with 47.6% receiving RT. In total, 316 patients (0.52%) were diagnosed with MN; the cumulative incidence per 10,000 person-years was 10.6 vs 9.0 among RT-treated vs non-RT-treated women, respectively (p = .004); the increased risk of subsequent MN persisted in the adjusted analysis (hazard ratio = 1.36, 95% confidence interval: 1.03–1.80). The results were consistent in multiple sensitivity analyses.</p><p>Conclusions</p><p>Our data suggest that RT is associated with a significant risk of subsequent MN among older breast cancer survivors, though the absolute risk increase is very small. These findings suggest the benefits of RT outweigh the risks of development of subsequent MN.</p></div

The effect of radiation therapy on subsequent myeloid neoplasm (MN) after breast cancer.

<p>The effect of radiation therapy on subsequent myeloid neoplasm (MN) after breast cancer.</p

The effect of radiation therapy on subsequent myeloid neoplasms after breast cancer according to data source (N = 60,426).

<p>The effect of radiation therapy on subsequent myeloid neoplasms after breast cancer according to data source (N = 60,426).</p

Characteristics of study sample, stratified by receipt of radiation therapy.

<p>Characteristics of study sample, stratified by receipt of radiation therapy.</p

Adjusted cumulative incidence of myeloid neoplasm (MN) for localized breast cancer among older women stratified by receipt of radiation therapy.

<p>Source: SEER-Medicare. Source: SEER-Medicare. Abbreviations: RT: Radiation Therapy, BCS: Breast Conserving Surgery, MDS: myelodysplastic syndromes, AML: acute myeloid leukemia. Model adjusted for age, race, marital status, income, education, metropolitan status, comorbidity, disability, anemia, stage, grade, tumor size, node involvement, tumor laterality, hormone receptors, receipt of BCS, Medicaid coverage, year of breast diagnosis and geographic region.</p