Background: Evidence suggests that there are clinical features associated with a less favorable prognosis among patients with HR+/HER2- metastatic breast cancer (MBC) such as metastases to non-bone sites, including liver and lung, and negative progesterone receptor (PgR-) status. The objective of this study was to compare baseline characteristics and outcomes between those with and without these clinical factors among a cohort of HR+/HER2- MBC patients treated with a CDK4&6 inhibitor (CDK4&6i). Methods: This was a retrospective analysis of the Flatiron Health electronic health records-derived database for US patients diagnosed with MBC between 1/1/2011 and 9/30/2017. The study included a random sample of patients with HR+/HER2- MBC who were treated with a CDK4&6i on or after 6/30/2016. Baseline variables, including demographics, comorbidities, and sites of metastasis, were recorded at start of the first CDK4&6i containing line of therapy in the metastatic setting on or after this date. Dates of real-world progression were abstracted from patient charts. Descriptive statistics and appropriate statistical tests were used to compare baseline characteristics between patients with or without select clinical factors associated with unfavorable outcomes. In patients who received a CDK4&6i-based therapy, Kaplan–Meier methods and univariable Cox proportional hazards models were used to assess real-world progression free survival (rwPFS) by line from start of line to the date of first progression or death within line (unadjusted for treatment and other potential confounders). Results: 518 patients were included in this study. Median age at metastatic diagnosis was 66y (IQR; 59-73y); 99% female and 11.4% had PgR- status. At baseline, 20.5%, 46.3%% and 65.8% of patients had liver, visceral (defined as liver and/or lung), and non-bone only metastases, respectively. Among a total of 207 patients who received a CDK4&6i as initial therapy in the metastatic setting, 69.1% received it in combination with an aromatase inhibitor, 29.5% received it in combination with fulvestrant, and 1.4% as monotherapy. Within the same group, 58 had disease progression or died during first line (1L); median rwPFS measured from start of 1L was not reached (95% CI: 10.7 months, NA). Univariable analyses revealed the presence of liver metastases was associated with a higher risk of progression or death compared to no liver metastases (HR: 2.04, 95% CI: 1.13 - 3.68). Having non bone-only metastases was associated with a higher risk of progression or death compared to having bone-only metastases (HR: 2.23, 95% CI: 1.20 – 4.15). Univariable analyses did not reveal any statistically significant differences in first-line rwPFS by PgR status or presence of visceral metastases. Results from other lines of therapy are forthcoming. Conclusion: In a real world data set, and consistent with prior prospective data, presence of liver and non-bone only metastases were associated with a higher risk of progression among patients with HR+/HER2- MBC receiving initial therapy with a CDK4&6i. The heterogeneity of prognoses among this population reinforces the need to consider these clinical features in treatment decisions for optimal patient outcomes. Citation Format: Saverno KR, Carter GC, Li L, Battiato LA, Huang Y-J, Smyth EN, Price GL, Sheffield KM, Baxi SS, Kuk D, Seidman AD. Influence of prognostic factors on outcomes among metastatic breast cancer patients treated with CDK4&6 inhibitors in routine clinical practice [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-38.

Background: In the MONARCH 3 trial, abemaciclib plus an aromatase inhibitor (AI) significantly improved progression free survival and overall response rate with a generally tolerable safety profile compared to placebo plus AI. Here we report patient-reported outcomes (PRO) including health-related quality of life (Qol), functioning, and symptoms. Methods: MONARCH 3 was a double-blind, randomized phase III study of abemaciclib or placebo plus an AI in 493 post-menopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer with no prior systemic therapy in the advanced setting. Two European Organization for Research and Treatment of Cancer (EORTC) questionnaires were included: Quality of Life Questionnaire (QLQ)-Core 30 (C30) and the EORTC QLQ-Breast 23 (BR23) that were assessed at baseline, every 2 cycles through cycle 19, then every 3 cycles until treatment discontinuation, and at short-term follow up. Higher scores on functional and health status/QoL outcomes indicate higher/better levels of functioning or health; conversely higher scores on symptom outcomes indicate higher/worse levels of symptom burden. Between-arm comparisons of change from baseline were conducted using mixed model methods. Statistical significance was set at 0.05 and clinical meaningfulness was set at ≥10 points on a 0-100 scale1. Results: PRO completion rates were >91% through cycle 19; duration of treatment was longer for abemaciclib plus AI patients (median number of cycles 19 vs.15). Compared to the placebo arm, diarrhea PRO scores in the abemaciclib arm showed a clinically (18.68 points) and statistically significant (p<0.001) increase/worsening. By-cycle analysis showed group mean diarrhea scores returned to near-baseline levels post-therapy. Other symptom PROs showed statistically significant (<0.05) but not clinically meaningful differences; fatigue (4.96; p=0.004), systemic therapy side effects (4.48, p<0.001), appetite loss (4.03; p=0.034), and nausea/vomiting (2.77; p=0.013). These results were consistent with the investigator-reported treatment emergent adverse events (TEAEs). Several non-symptom results were also statistically significant but not clinically meaningful including global health/health status (-4.36; p=0.003), role function (-4.25; p=0.025), social function (-3.41, p=0.047), and body image (-5.11, p=0.009). No statistically significant between-treatment differences were observed for physical, emotional, and cognitive functioning or for symptoms of pain, dyspnea, insomnia, constipation, or financial difficulties. Conclusions: The addition of abemaciclib to an AI resulted in clinically and statistically significant changes in diarrhea without clinically meaningful differences in other symptom scores. Increased GI-related symptoms were consistent with the manageable, reversible AE profile; the highest symptom burden was reported during early visits. No clinically meaningful differences in global health status or functional scores were observed. ClinicalTrials.gov: NCT02246621 Reference: 1. Osoba D et al. J Clin Oncol 2002;20(14):3106-13. Citation Format: Goetz MP, Johnston S, Martin M, Tokunaga E, Park IH, Huober J, Toi M, Price GL, Boye M, Li L, Forrester T, Gainford C, Gable J, Carter GC, Sood A, DiLeo A. Health-related quality of life in MONARCH 3: Abemaciclib plus an aromatase inhibitor as initial therapy in women with HR+, HER2- advanced breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-16-01.

Background In MONARCH 1 (NCT02102490), abemaciclib demonstrated promising single-agent activity and tolerability in a population of heavily pretreated women with refractory HR+, HER2- metastatic breast cancer (MBC).1 Confirmed objective response rate (ORR) was 19.7% (95% CI: 13.3, 27.5) and at 18 months minimum follow-up median overall survival (OS) was 22.3 months. Due to the single-arm trial design of MONARCH 1, there is a need to view these results in clinical context relative to available treatment options. This study compared the OS results of abemaciclib in MONARCH 1 vs that in a real-world single-agent chemotherapy cohort with similar patient and disease characteristics. Methods MONARCH 1 study design and key eligibility criteria were previously described.1 The real-world cohort was based on Flatiron Health electronic health records-derived, nationally representative (USA-based) database comprising patient-level structured and unstructured data, curated via technology-enabled abstraction, for patients with MBC between January 1, 2011 through February 28, 2018. A real-world single-agent chemotherapy cohort was created based on the key eligibility criteria of MONARCH 1 and included patients diagnosed with HR+, HER2- MBC who received single-agent chemotherapy (eribulin, capecitabine, gemcitabine, or vinorelbine) following 1-2 prior chemotherapy regimens in the metastatic setting, had an ECOG PS of 0-1, and no prior CDK4 & 6 therapy. The index date was the start of the eligible single-agent chemotherapy, and patients were followed from the index date until date of death, loss to follow-up, or end of the database, whichever occurred earlier. OS results were adjusted using 2 methods (Mahalanobis distance matching and entropy balancing with bootstrapping) to account for baseline demographic and clinical differences between the real-world and trial cohorts. Results A real-world cohort (n=281) with eligibility criteria similar to the MONARCH 1 population (n=132) was identified. A subsequent matching based on Mahalanobis distance was performed to match MONARCH 1 population (n=108) with the real-world cohort (n=108). The matched cohorts demonstrated similar patient and disease characteristics. Median OS was 22.3 months in the abemaciclib arm vs 13.6 months in the matched cohort with an estimated hazard ratio (HR) of 0.54 (95% CI: 0.37, 0.77). Results of a sensitivity analysis performed using entropy balancing were consistent with an adjusted median OS of 12.7 months in the real-world cohort (n=281)with HR of 0.57 (95% CI from bootstrapping: 0.44, 0.78). Conclusion Methodological advances to adjust for potential biases, and improvements in data quality, have evolved enabling the ability to leverage a real-world cohort as an external comparator arm. This study demonstrates the ability to create a real-world chemotherapy cohort suitable to serve as a comparator for MONARCH 1. These exploratory results suggest a survival advantage and adequately place the clinical benefit of abemaciclib monotherapy in clinical context. References Dickler et al, CCR 2017 Citation Format: Rugo H, Dieras V, Cortes J, Patt D, Wildiers H, O'Shaughnessy J, Zamora E, Yardley DY, Carter GC, Sheffield KM, Li L, Andre VA, Derbyshire RE, Li XI, Frenzel M, Huang Y-J, Dickler MN, Tolaney SM. Real-world survival of heavily pretreated patients with refractory HR+, HER2- metastatic breast cancer receiving single-agent chemotherapy - A comparison with MONARCH 1 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-19.

Background Hormone receptor positive (HR+)/HER2– tumors are the most common subtype among patients with metastatic breast cancer (MBC). Several newer therapeutic options have become available over the last decade, but little is known about the real-world treatment patterns and health care resource use (HCRU) in privately insured women with HR+/HER2– MBC. Methods An analysis of Truven MarketScan databases containing medical and drug utilization and productivity data from nearly 350 US payers was conducted. Patients aged 18-64 years with an ICD-9 diagnosis code of breast cancer along with ≥2 claims for secondary malignancy between 2007 and 2013 were selected. HR+/HER2– patients were identified based on receipt of endocrine therapy (ET) and absence of HER2-targeted therapies. Use of cancer-directed treatments following MBC diagnosis was analyzed. Treatment characteristics were examined by line of therapy (LOT). Average monthly all-cause and MBC-related HCRU were descriptively assessed. Results A total of 5,563 women with HR+/HER2– MBC (mean [SD] age, 54 [7.8] yrs) met the selection criteria. Overall, 97% of the total sample received ≥1 cancer-directed treatment. The most common treatment was ET (85%), followed by chemotherapy (CT) (70%), radiation (62%), and surgery (11%). Treatment patterns for CT alone and ET alone, including the top regimens by LOT, are presented in Table 1. Among those receiving a second LOT, nearly 44% switched to CT in the second line after having received ET alone in the first line. During the study follow-up, 56% of patients had ≥1 all-cause inpatient admission, 49% had ≥1 all-cause emergency department visit, and 9% had a hospice admission. Table 1. Treatment patterns by LOT in patients with HR+/HER2- MBCLine 1 Line 2 Line 3 Line 4 n=5,179 (93%)* n=2,900 (52%)* n=1,608 (29%)* n=882 (16%)*  n (%) n (%) n (%) n (%)ET Alone3265 (63)ET Alone1468 (51)ET Alone534 (33)ET Alone217 (25)Anastrozole895 (27)Fulvestrant354 (24)Fulvestrant138 (26)Fulvestrant65 (30)Letrozole782 (24)Tamoxifen258 (18)Exemestane89 (17)Exemestane44 (20)Tamoxifen577 (18)Exemestane239 (16)Letrozole82 (15)Tamoxifen25 (12)Fulvestrant428 (13)Anastrozole239 (16)Tamoxifen82 (15)Letrozole20 (9)Exemestane299 (9)Letrozole197 (13)Anastrozole65 (12)Anastrozole14 (6)CT Alone1533 (30)CT Alone1057 (36)CT Alone818 (51)CT Alone505 (57)Paclitaxel413 (27)Capecitabine331 (31)Capecitabine265 (32)Capecitabine140 (28)Capecitabine286 (19)Paclitaxel224 (21)Paclitaxel156 (19)Paclitaxel93 (18)Cyclophosphamide-Doxorubicin → Taxane93 (6)Gemcitabine63 (6)Gemcitabine70 (9)Vinorelbine55 (11)Cyclophosphamide-Docetaxel82 (5)Docetaxel46 (4)Vinorelbine54 (7)Gemcitabine52 (10)Carboplatin-Paclitaxel77 (5)Vinorelbine46 (4)Doxorubicin45 (6)Doxorubicin34 (7)*Out of total 5,563 patients. Only top CT and ET regimens are listed. Conclusions A substantial decrease in the use of ET, with simultaneous increase in the use of CT, was observed as patients progressed to subsequent LOTs. Nearly half of those receiving ET alone in the first LOT switched to CT in the second LOT, suggesting a need for more effective non-CT treatments to bridge unmet therapeutic needs in this patient population. Citation Format: Goyal RK, Carter GC, Nagar SN, Smyth EN, Price GL, Huang Y-J, Bromund JL, Li L, Schilder JM, Davis KL, Kaye JA. Treatment patterns and resource utilization among patients with HR+/HER2– metastatic breast cancer in a privately insured US population [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 P5-08-18.

Background Therapeutic advances in metastatic breast cancer (MBC) over the last decade have led to several novel agents for the treatment of patients with hormone receptor positive (HR+)/HER2– MBC. However, current literature has little data on real-world treatment patterns and health care resource use, particularly among elderly women with HR+/HER2– MBC in the United States Medicare population. Methods A retrospective analysis of patients aged ≥66 years diagnosed with MBC during 2007 to 2011 was conducted using the SEER-Medicare database. Patients' HR and HER2 status was obtained from the SEER registry data. For patients with no HER2 data available, HER2− disease was determined based on the absence of HER2-targeted therapies within 12 months of diagnosis. Health care utilization and treatment patterns after MBC diagnosis were examined. Use of cancer-directed therapies, including chemotherapy (CT) and endocrine therapy (ET), were descriptively analyzed by line of therapy (LOT). Results A total of 3,622 women with HR+/HER2– MBC (mean [SD] age, 77 [7.3] years) were included. Over 90% of women received ≥1 cancer-directed treatment after MBC diagnosis, with ET being the most common (77%), followed by CT (50%), radiation (48%), and surgery (19%). Treatment with ET alone trended downward across LOTs, from 74% in the first LOT to 36% in the fourth LOT, with a corresponding increase in treatment with CT alone from 21% to 46% (Table 1). Among those receiving a second LOT, nearly 26% switched to CT in the second line after having received ET alone in the first line. Table 1. Pharmaceutical treatment patterns by line of therapy among patients diagnosed with HR+/HER2– MBC (n = 3622)First-Line Second-Line Third-Line Fourth-Line N = 2,981 (82%)* N = 1,449 (40%)* N = 750 (21%)* N = 356 (10%)*  n (%) n (%) n (%) n (%)ET Alone2215 (74)ET Alone973 (67)ET Alone381 (51)ET Alone127 (36)Anastrozole893 (40)Fulvestrant282 (29)Fulvestrant99 (26)Fulvestrant38 (30)Letrozole602 (27)Exemestane190 (20)Exemestane76 (20)Tamoxifen27 (21)Tamoxifen253 (11)Anastrozole162 (17)Tamoxifen71 (19)Exemestane25 (20)Fulvestrant243 (11)Tamoxifen152 (16)Anastrozole46 (12)Anastrozole13 (10)Exemestane156 (7)Letrozole107 (11)Letrozole38 (10)Exemestane-FulvestrantN/ACT Alone639 (21)CT Alone336 (23)CT Alone264 (35)CT Alone165 (46)Paclitaxel136 (21)Paclitaxel76 (23)Paclitaxel78 (30)Paclitaxel39 (24)Cyclophosphamide-Docetaxel72 (11)Gemcitabine57 (17)Gemcitabine46 (17)Gemcitabine32 (19)Cyclophosphamide-Doxorubicin → Taxane69 (11)Docetaxel28 (8)Vinorelbine31 (12)Vinorelbine21 (13)Carboplatin-Paclitaxel43 (7)Vinorelbine27 (8)Docetaxel22 (8)Doxorubicin17 (10)Docetaxel39 (6)Doxorubicin21 (6)Doxorubicin21 (8)DocetaxelN/AN/A = not available (in accordance with the SEER-Medicare data use agreement, data for categories with cell size less than 11 are suppressed). *Out of total 3,622 patients. Note: Percentages do not add up to 100% as only the top CT and ET regimens are listed. Conclusions ET was the most common first-line treatment for elderly women with HR+/HER2– MBC in this study period. However, as patients progressed from first to fourth LOT, the proportion of patients treated with ET decreased substantially. Citation Format: Goyal RK, Carter GC, Nagar SN, Smyth EN, Price GL, Huang Y-J, Bromund JL, Li L, Schilder JM, Davis KL, Kaye JA. Treatment patterns and resource utilization among elderly Medicare patients with HR+/HER2– metastatic breast cancer [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 P5-08-19.