Y Hao

Abstract P1-14-03: Chemotherapy and endocrine therapy treatment patterns among patients with hormone receptor positive (HR+)/HER2 negative advanced breast cancer

Background: National Comprehensive Cancer Network breast cancer guidelines suggest optimized sequencing of endocrine therapy prior to chemotherapy use for patients who are HR+/HER2-, but it is unclear how those recommendations translate into clinical practice. This study examined sequencing of endocrine and chemotherapy treatment to better understand real-world treatment patterns for HR+/HER2- advanced breast cancer. Methods: This retrospective study examined physician-reported clinical data on patients with breast cancer (BC) linked to medical and pharmacy claims (2008-2012) from a large national US health plan. Patients included in the study had HR+ and HER2- status. Advanced cancer cohorts included patients who were stage IV (SIV) at initial diagnosis, or who developed metastases following initial diagnosis (MET). The first date of diagnosis of advanced cancer or date of metastases following initial diagnosis was designated as index date. Health plan enrollment for 3 months pre- and ≥12-months post- index date was required; patients who died within 12 months after index date and were continuously enrolled were retained. A 3-month baseline period assessed prior treatment; variable post-index follow-up (until disenrollment or Oct 2012) assessed patterns of endocrine and chemotherapy. Results: Of 317 MET patients, 50% initiated chemotherapy after index date without prior endocrine treatment (CH). Remaining patients (OT) used only endocrine therapy (30%), endocrine therapy prior to chemotherapy (17%), or neither endocrine nor chemotherapy (3%). Compared with OT patients, CH patients were younger (50 vs. 55 years, P Conclusions: In this population of patients with HR+/HER2- advanced breast cancer, a large proportion initiated chemotherapy without prior endocrine therapy. This group of patients might otherwise benefit from a longer progression free period with tolerable toxicity from endocrine therapy. Further investigation of whether a subgroup of these patients started chemotherapy in the adjuvant setting is warranted. For those starting chemotherapy without prior endocrine therapy, understanding treatment sequencing and patient characteristics will help illuminate the extent to which patterns adhere to NCCN guidelines. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-14-03.

Abstract P3-06-09: Survival among patients with hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer: A real-world observational study

Background: Little is known about real-world outcomes for patients with HR+/HER2- advanced breast cancer. This study examined mortality outcomes, and in particular variations across patients with different stages of cancer and different sequencing of endocrine and chemotherapy treatments. Methods: This retrospective study linked medical and pharmacy claims (2008-2012) from a large national US health plan with a proprietary clinical cancer database containing physician-reported clinical data on patients with breast cancer. Patients included in the study had HR+ and HER2- status, and had stage III (S3) or IV (S4) cancer at initial diagnosis, or had developed metastases following initial diagnosis (MET). The first date of diagnosis of advanced cancer or the first date of metastases following initial diagnosis was designated as the index date. Health plan enrollment for 3 months pre- and ≥12-months post- index date was required; patients who died within 12 months after index date and were continuously enrolled in the health plan were retained. A 3-month baseline period assessed prior treatment; a variable follow-up (until disenrollment or 31 Oct 2012) assessed patterns of endocrine and chemotherapy treatments following the index date. Patient mortality was identified via a combination of Social Security mortality data and patient hospital discharge status from claims data. Chi-square tests compared proportions and t-tests compared means. Results: The study population included 263 S3, 71 S4, and 317 MET patients. Average age at index date was 51.9 years for S3, 54.4 years for SIV, and 52.8 years for MET patients (P = 0.080). Over the entire observable follow-up, 3.4% of S3 (17 per 1000 patient-years), 22.5% of S4 (119 per 1000 patient years), and 10.7% of MET patients (22 per 1000 patient years) died (P≤0.010 for comparisons). Mortality over the 1-year after index date was 1.1%, 12.7%, and 5.1% in the S3, S4, and MET groups respectively (P Conclusions: Among patients with HR+/HER2- advanced breast cancer, mortality rates varied by stage of disease, and length of survival varied across patients pre-treated with endocrine therapy prior to chemotherapy compared with other patients. Further investigation of drivers behind differences in mortality may reveal the extent to which initial disease severity and sequencing of chemotherapy and endocrine therapy drive these variations. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-06-09.

Abstract P4-22-19: Time on treatment of everolimus versus endocrine monotherapy or chemotherapy for early-line treatment of HR+/HER2- metastatic breast cancer: A retrospective chart review study in the US

Background: Among postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor-2-negative (HR+/HER2-) metastatic breast cancer (mBC) whose disease progressed on a non-steroidal aromatase inhibitor (NSAI), everolimus-based therapy (EVE), different endocrine monotherapies (ET mono), and chemotherapies (CT) are commonly used. Time on treatment is an outcome primarily determined by a therapy9s combined efficacy and safety profile. This study assessed the real-world time on treatment (TOT) among patients receiving these treatments in early-line (i.e., 1st and 2nd) settings. Methods: A nationwide sample of postmenopausal HR+/HER2- mBC patients treated by community oncologists in the US was included in this retrospective chart review. Eligible patients for this study were required to fail NSAI and then receive EVE, ET mono or CT (index therapy) as an early-line therapy for mBC between July 1, 2012 and April 15, 2013. TOT was measured from index therapy initiation to physician-reported treatment discontinuation and compared among treatment groups using Kaplan-Meier analyses with log-rank tests and Cox proportional hazards models adjusting for the line of therapy and baseline characteristics including recurrent or de novo disease status, age, race, insurance type, Charlson comorbidity index, sites of metastases (e.g., bone, any other visceral site), ECOG performance status, previous CT treatment in the mBC setting, and duration from the initiation of the last adjuvant ET to mBC diagnosis. Results: A total of 145 patients treated with EVE, 217 patients treated with ET mono, and 102 patients treated with CT were included in the analysis. Baseline characteristics among the three treatment groups were similar, although EVE-treated patients had higher burden of metastases relative to ET mono-treated patients, but lower burden relative to CT-treated patients. TOT was longer among EVE-treated patients than ET mono- and CT- treated patients (log-rank tests: p=0.01 and p Conclusions: This real-world US chart review study of postmenopausal women with HR+/HER2- mBC showed that patients receiving EVE in line 1 or 2 experienced significantly longer TOT than those receiving ET mono or CT. Citation Format: Li N, Ohashi E, Koo V, Xie J, Hao Y, Tang DH. Time on treatment of everolimus versus endocrine monotherapy or chemotherapy for early-line treatment of HR+/HER2- metastatic breast cancer: A retrospective chart review study in the US [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-22-19.

Abstract P4-13-14: Time on treatment of everolimus, fulvestrant, and capecitabine for the treatment of HR+/HER2- metastatic breast cancer: A retrospective claims study in the US

Background: Treatment guidelines for hormone receptor-positive/human epidermal growth factor receptor-2-negative (HR+/HER2-) metastatic breast cancer (mBC) recommend extending the time on treatment (TOT) of endocrine therapy (ET) prior to the initiation of chemotherapy (CT) to avoid its serious side effects and preserve patients9 quality of life. Everolimus-based therapy (EVE), fulvestrant monotherapy (FUL mono), and capecitabine monotherapy (CAP mono) are among the latest ET and CT agents approved for the treatment of HR+/HER2- mBC in the US. This retrospective claims analysis compared TOT among HR+/HER2- mBC patients who received EVE versus those who received FUL mono or CAP mono respectively. Methods: Postmenopausal women with HR+/HER2- mBC who initiated ≥ 1 new line of therapy for mBC between 7/20/2012 (the approval date of EVE, the latest of all three therapies) and 3/31/2014 (which allowed for ≥ 3 months of potential follow-up) after a non-steroidal aromatase inhibitor were identified from the MarketScan and PharMetrics databases (2002Q1-2014Q2) using an algorithm adapted from the literature. Treatment discontinuation was defined as a treatment gap of ≥ 60 days. Patients9 lines of therapies were classified into mutually-exclusive regimen groups (i.e., EVE, FUL mono, and CAP mono) and followed until discontinuation of the line of therapy, end of insurance eligibility, or data cut-off (06/30/2014). Patients who did not discontinue their treatment were censored at the end of follow-up. TOT was compared between EVE versus FUL mono and versus CAP mono using Kaplan-Meier (K-M) analyses with log-rank tests and multivariable Cox models adjusting for the line of therapy and differences in patient characteristics, including age, insurance type, de novo vs non-de-novo mBC, prior use of CT for mBC, sites of metastases (e.g., bone, brain, and visceral), and Charlson comorbidity index. Results: Across the first four lines of therapies for mBC, a total of 940 EVE, 953 FUL mono, and 721 CAP mono regimens were included. Based on the different lines of therapies, the K-M estimators of median TOT ranged from 5.5 to 7.2 months for EVE, 4.9 to 8.4 months for FUL mono, and 3.5 to 6.0 months for CAP mono. Pooling all lines of therapies, EVE was associated with significantly longer TOT compared to FUL mono (multivariable-adjusted hazard ratio [HR] = 0.87, 95% confidence interval [CI]: 0.76-0.99) or CAP mono (multivariable-adjusted HR = 0.73, 95% CI: 0.64-0.83). Similar results were observed in each line of therapy. Conclusions: This real-world US claims study of postmenopausal women with HR+/HER2- mBC showed that patients receiving EVE experienced significantly longer TOT than those receiving FUL mono or CAP mono, suggesting a comparative advantage of EVE in extending the duration of ET. Citation Format: Li N, Hao Y, Kageleiry A, Peeples M, Fang A, Koo V, Guerin A. Time on treatment of everolimus, fulvestrant, and capecitabine for the treatment of HR+/HER2- metastatic breast cancer: A retrospective claims study in the US. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-13-14.

Abstract P4-13-13: Real-world effectiveness of everolimus versus endocrine monotherapy or chemotherapy in HR+/HER2- metastatic breast cancer patients with liver metastasis or multiple metastatic sites

Background: Liver metastasis and multiple metastatic sites are associated with higher risk of progression or death among women with hormone receptor-positive, human epidermal growth factor receptor-2-negative (HR+/HER2-) metastatic breast cancer (mBC). Traditional treatments, like endocrine monotherapy (ET mono) or chemotherapy (CT), have limited effectiveness in these high-risk patients. Everolimus-based therapy (EVE) is a new treatment option with different mechanism of action. This study examined the real-world comparative effectiveness of EVE vs. ET mono or CT in patients with liver metastasis or multiple metastatic sites. Methods: A sample of postmenopausal women with HR+/HER2- mBC was obtained through a retrospective chart review of community-based oncology practices in the US. All patients initiated EVE, ET mono, or CT (defined as the index therapy) for mBC between July 2012 and April 2013 after the failure of a non-steroidal aromatase inhibitor. Patients with liver metastasis and those with multiple metastatic sites (i.e., ≥2 non-lymph-node metastases) at the index therapy initiation were analyzed separately. In each group, progression-free survival (PFS) and time on treatment (TOT) were compared between EVE vs. ET mono or CT, respectively, using Kaplan-Meier analyses with log-rank tests and Cox proportional hazards models adjusting for patient and disease characteristics, such as age, mBC type, performance status, tumor burden, and prior treatment. Patients without an event were censored at the last follow-up. Results: A total of 202 patients had liver metastasis, including 82 treated with EVE, 49 with ET mono, and 71 with CT. EVE patients had more severe mBC than ET mono patients and less severe mBC than CT patients, as indicated by proportion of patients receiving prior CT for mBC and tumor burden. Compared with ET mono, EVE was associated with significantly longer PFS (log-rank test p=0.049; hazard ratio (HR)=0.48, 95% confidence interval (CI): 0.27-0.87) and TOT (log-rank test p=0.054, HR=0.49, 95% CI: 0.28-0.86). Similarly, compared with CT, EVE was associated with significantly longer PFS (log-rank test p=0.024, HR=0.76, 95% CI: 0.44-1.32) and TOT (log-rank test p A total of 265 patients had multiple metastatic sites, including 100 treated with EVE, 79 with ET mono, and 86 with CT. Similarly, EVE patients had more severe mBC than ET mono patients and less severe mBC than CT patients, as indicated by tumor burden. Compared with ET mono, EVE was associated with significantly longer PFS (log-rank test p=0.043, HR=0.62, 95% CI: 0.41-0.95) and TOT (log-rank test p=0.054, HR=0.64, 95% CI: 0.42-0.97). Compared with CT, EVE was also associated with longer PFS (log-rank test p=0.004, HR=0.60, 95% CI: 0.39-0.92) and TOT (log-rank test p Conclusion: In this retrospective chart review of HR+/HER2- mBC patients, EVE was associated with significantly longer PFS and TOT compared with ET mono or CT in high-risk patients with liver metastasis or multiple metastatic sites. Citation Format: Li N, Hao Y, Lin PL, Koo V, Ohashi E, Wu EQ, Xie J. Real-world effectiveness of everolimus versus endocrine monotherapy or chemotherapy in HR+/HER2- metastatic breast cancer patients with liver metastasis or multiple metastatic sites. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-13-13.

Abstract P2-08-20: Clinical outcomes among HR+/HER2- metastatic breast cancer patients with multiple metastatic sites

Background: Hormone receptor-positive, human epidermal growth factor receptor-2-negative (HR+/HER2-) is the most common type of metastatic breast cancer (mBC). While overall the prognosis among these patients is poor with short progression-free survival (PFS) and overall survival (OS), those with multiple metastatic sites (multiple mets) may have even worse clinical outcomes due to multiple organ involvement. This real-world study examined clinical outcomes among HR+/HER2- mBC patients with multiple mets. Methods: In this retrospective chart review, a sample of postmenopausal women with HR+/HER2- mBC was collected from community-based oncology practices in the US. Patients were required to have failed a non-steroidal aromatase inhibitor and later initiated a new treatment (defined as the index therapy) for mBC between July 1, 2012 and April 15, 2013. Patients were classified into two mutually exclusive groups: multiple mets or single metastatic site (single met), based on the number of non-lymph-node metastatic sites at index therapy initiation. PFS, time on treatment (TOT), and OS were compared between the two study groups using Kaplan-Meier analyses with log-rank tests and multivariable Cox proportional hazards models adjusting for baseline characteristics, including age, race, insurance, mBC type, and months from initiation of last adjuvant endocrine therapy to mBC diagnosis, index therapy type, index therapy line, adjusted Charlson comorbidity index (CCI), Eastern Cooperative Oncology Group (ECOG) performance status, and prior chemotherapy for mBC. Patients without an event were censored at the last follow-up. In addition, separate Cox proportional hazard models were conducted including an interaction term between line of therapy and study group to assess the impact of multiple mets on clinical outcomes across different lines of therapy. Results: A total of 408 patients in the single met group and 291 patients in the multiple mets group were included. Patients with multiple mets had worse ECOG performance status and a higher rate of prior chemotherapy use for mBC compared with patients in the single met group. Relative to patients with single met, patients with multiple mets were associated with significantly shorter PFS (log-rank test p Conclusion: Among HR+/HER2- mBC patients, those with multiple mets had significantly worse clinical outcomes, highlighting substantial disease burden and unmet need for more efficacious treatment for these patients. Citation Format: Xie J, Hao Y, Li N, Lin PL, Ohashi E, Koo V, Wu EQ. Clinical outcomes among HR+/HER2- metastatic breast cancer patients with multiple metastatic sites. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-20.

Incidence of breast cancer among women in the United States, by human epidermal growth factor receptor-2 status: An analysis of National Registry data 2010.

112 Background: Few studies of breast cancer (BC) incidence by human epidermal growth factor receptor 2 (HER2) status exist as it is not routinely collected in population-based registries. This study used newly collected registry data to evaluate incidence of BC by HER2 status. METHODS The Surveillance, Epidemiology, and End Results (SEER) Program is a system of tumor registries designed to track cancer incidence and survival, covering about 25% of the US population. The SEER*Stat Database used for this analysis provides summary prevalence/incidence rates, frequencies, and case statistics. We evaluated age-adjusted (to the 2000 US population) incidence (number of cases per 100,000 females) of newly diagnosed female BC during 2010, by HER2 status, stratified by age, race, and stage at diagnosis. Cases with unknown values for any stratifier were excluded. Patients were classified as HER2+/HER2- based on a new HER2 status variable collected beginning in 2010. RESULTS There were 49,347 cases of newly diagnosed female BC in 2010 (7,331 [14.9%] HER2+ and 42,016 [85.1%] HER2-). Annual incidence of HER2+ BC was lower than incidence of HER2- BC (15.5 vs. 87.9 per 100,000 females; p<0.01). Incidence was highest among patients aged 65-74 years (42.4 [HER2+] and 318.1 [HER2-]), followed by 75+ (34.3 and 292.2), 45-64 (33.7 and 170.4) and under 45 (4.8 and 17.5). Incidence rates by race were as follows: Blacks (17.1 [HER2+] and 83.1 [HER2-]), Whites (15.5 and 91.3), Asian or Pacific Islanders (14.9 and 65.5), and American Indian/Alaska Natives (7.3 and 37.1). Incidence rates were highest for less advanced stages of BC: Stage I (6.1 [HER2+], 45.9 [HER2-]), II (5.5, 28.1), III (2.7, 9.9), and IV (1.2, 4.0). Differences in incidence rates across all strata among HER2+ and HER2- patients were statistically significant (p<0.01). CONCLUSIONS This analysis is among the first to utilize the new SEER HER2 status variable. About 15% of newly diagnosed BC cases reported to SEER in 2010 were HER2+. Differences in incidence across age and stage followed a similar pattern for both HER2+ and HER2- BC, while slight differences by race were observed. Further outcomes studies by HER2 status are warranted.

Abstract P3-06-11: Disease and treatment characteristics of a large insured female population with advanced or metastatic breast cancer by receipt of HER2-targeted agents

This retrospective administrative claims study of women diagnosed with advanced or metastatic breast cancer (BC) compared clinical histories and BC treatment by receipt of HER2- targeted agents (2TA), disease stage, and age group. Women ≥ 18 years, diagnosed with stage III or IV BC were selected from the 2008-2012 Truven Health MarketScan databases using ICD-9-CM codes on non-diagnostic medical claims corresponding to BC and local or distant metastases; date of first metastasis was the index date. Patients were followed until the earliest of end of enrollment, inpatient death or 12/31/2012. Those with <12 months continuous enrollment (CE) or non-BC primary cancers pre-index, or HIV or pregnancy anytime were excluded. 2TA was defined as ≥1 medical or pharmacy claim for trastuzumab or lapatinib in the pre- or post-index periods. Study cohorts were women ± 2TA use, 2TA users with stage III and IV BC, and 2TA users age 18-44, 45-64, or 65+ at index. Index demographics, pre-index BC and clinical histories, and post-index BC treatments were compared using t-tests, one-way ANOVA, and chi-square statistics. Of 30,660 eligible women, 14.4% received 2TA at sometime. Compared to non-2TA patients those with 2TA were younger (mean (SD) age 55 (11) vs. 59 (13) years; p≤0.001) and had significantly lower comorbidity burden. While pre-index BC was similar (48% each), 2TA patients had higher rates of pre-index BC surgery (20% vs. 17%), adjuvant/neoadjuvent chemotherapy (74% vs. 53%), radiation treatment (12% vs. 10%), and lower non-2TA biologics use (0% vs. 3%), all p<0.005. Of the 2TA cohort with pre-index BC, 58% used 2TA pre-index. Also among 2TA patients, 57% had Stage III BC at index and 18% were 18-44, 68% 45-64 and 15% 65+. Pre-index BC diagnosis differed by index BC stage (30% III vs. 73% IV) and increased with age (44% 18-44, 48% 45-64, 54% 65+), both p<0.001. Of those with ≥ 3 months CE post-index, 2TA users had higher rates, p<0.001 of BC surgery (53% vs. 47%), radiation (65% vs. 54%) and non-2TA antineoplastic treatment (AT: 89% vs. 83%), compared to non-2TA patients. Of those treated, 2TA users had a higher rate of chemotherapy use (85% vs. 58%), but lower use rates of hormone therapy (56% vs. 78%) and non-2TA biologics (5% vs. 8%), all p<0.001. Receipt of post-index BC surgery was greater among 2TA stage III than stage IV patients (78% vs. 19%) and decreased with age (62% 18-44, 53% 45-64, 42% 65+), both p<0.001. Post-index, stage III 2TA patients were more likely (p<0.001) to have radiation therapy (72% vs. 56%), use 2TA agents post-index (97% vs. 91%), and other AT (92% vs. 84%) compared to stage IV 2TA patients. Radiation declined in the 2TA cohort post-index with increasing age (70%, 65%, 61%, p<0.001). 2TA and AT use also declined with increasing age but these did not reach statistical significance. Receipt of 2TA (vs. non-2TA) was significantly associated with younger age and receipt of pre- and post- BC treatments. Clinical history and BC treatment differences between these cohorts partly reflect differential treatment patterns of HER2- positive and HER2- negative BC patients. Treatment characteristics for the 2TA cohort differ by disease stage and age group. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-06-11.

Abstract P3-06-08: Patterns of health care utilization and costs by chemotherapy and endocrine therapy sequencing among patients with hormone receptor positive (HR+)/HER2- negative advanced breast cancer

Background: Little is known about health care costs and health services utilization of patients with HR+/HER2- advanced breast cancer, particularly in relation to the order in which patient receive endocrine and chemotherapy treatments. Methods: A proprietary database with physician-reported clinical data on patients with breast cancer was linked to medical and pharmacy claims (2008-2012) from a national US health plan. Patients included in the study had HR+ and HER2- status. Advanced cancer included stage III or IV (SIV) at initial diagnosis, or developed metastases following initial diagnosis. The first date of advanced cancer diagnosis or date of metastases following initial diagnosis was designated as the index date. Health plan enrollment for 3 months pre- and ≥12-months post- index date was required; patients who died within 12 months after index date and were continuously enrolled were retained. A 3-month baseline period assessed prior treatment; variable follow-up (until disenrollment or 31 Oct 2012) assessed patterns of endocrine and chemotherapy treatments following index date. All-cause and cancer-specific health care utilization and paid costs were assessed over 12-months following index date. Costs were calculated as per-patient-per-month (PPPM), and utilization measured as rates per patient-month. Cancer-related medication costs included drug costs for endocrine, chemotherapy, targeted therapy, and treatments for pain or chemotherapy-induced nausea/ vomiting. In addition, costs for anti-cancer systemic therapies (chemotherapy, endocrine, and targeted therapy) were calculated PPPM including costs for medication administration. Results: Of 651 study patients, 65% initiated chemotherapy prior to initiating endocrine therapy (CH). Remaining patients (OT) either had no chemotherapy (n = 132 endocrine only, n = 16 neither endocrine nor chemotherapy), or used endocrine therapy prior to chemotherapy (n = 77). Compared with OT, the CH group had more office (4.04 vs. 2.68 visits, P<0.001) and outpatient hospital visits (3.08 vs. 2.10 visits, P<0.001). In addition, 56% of CH vs. 41% of OT had inpatient hospital admissions during the follow-up (P<0.001; rate ratio 0.97, P = NS). Similarly, 60% of CH patients were admitted to emergency rooms vs. 51% of OT (P = 0.033; rate ratio 1.01, P = NS). Mean total all-cause health care costs varied (

Abstract P4-12-04: Initial treatment and survival among elderly breast cancer patients by receipt of human epidermal growth factor receptor 2-targeted therapy: An analysis of US national data 2006-2009

11,525 CH vs.