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: Recent advances in the treatment of hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) have contributed to increased overall survival (OS). Despite advances, MBC remains incurable and there is a subset of patients with clinical features that are associated with poorer prognosis. This study described the patient characteristics, treatment patterns, and outcomes of a cohort of US patients with HR+, HER2- MBC as a function of various factors associated with poor prognosis, including presence (vs. absence) of liver metastases (LM). Methods: This retrospective study used US community oncology electronic health record data from the Vector Oncology Data Warehouse. Eligible women who received systemic treatment for MBC, had a diagnosis of MBC in 2008 or later, and had completed at least three Patient Care Monitor (PCM) surveys, (a patient-reported outcomes survey collected as a part of clinical care), were included. OS was measured from the start of the first three regimen-based lines (1L, 2L and 3L) of treatment; patients without evidence of death were censored at the last observed visit. The statistical significance of differences in categorical and continuous variables between LM positive (LM+) and LM negative (LM-) were evaluated with chi-square (X2) tests, and t-tests, respectively. Kaplan-Meier and Cox analyses were applied to evaluate differences in OS by LM status and by line of therapy at the start of MBC treatment (unadjusted for treatment). Results: A total of 378 women, 98.4% residing in the South and 40.5% African-American, were included; 295 (78.0%) were LM- at the time of diagnosis. Following 1L, approximately 82.8% and 60.8% of patients received 2L and 3L, respectively. Patients with a LM+ status had a lower mean age (mean: 57.2, SD: 13.8 vs. 61.2, 13.1; p=0.016) and a higher percentage had a grade 3 tumor (36.1 vs. 24.7%; p=0.039) compared to patients with LM-status. Table 1 shows the OS results for 1L-3L. For all 3 lines, median OS for LM+ was shorter than the LM- median OS. LM+ patients had a poorer prognosis as they were more likely to have an OS event across 1L-3L compared to LM- patients. Conclusions: Among this community oncology cohort, median OS in 1L was 14 months shorter in LM+ patients compared to LM- patients. It is important to note that the sample size and selection criteria may limit generalizability of these results. Despite progress in treating women with MBC, treatment options are lacking for patients with less favorable prognosis, including those with LM. Other potential indicators of poor prognosis, such as high tumor grade, are being explored. Table 1.OS (months) by regimen-based line of therapy Measure Liver Mets (LM+) No Liver Mets (LM-) HR p-value 1L, # of Events/ # of Patients55/83168/295  Median (95% CI)23.9 (15.5-28.6)35.2 (30.1-42.3) <0.0001* Cox Hazard Ratio  1.93<0.0001 2L, # of Events/ # of Patients48/72149/241  Median (95% CI)16.6 (12.0-22.6)24.2 (21.3-29.0) 0.002* Cox Hazard Ratio  1.490.040 3L, # of Events/ # of Patients35/52118/178  Median (95% CI)11.5 (7.0-21.0)17.4 (14.7-20.0) 0.038* Cox Hazard Ratio  1.540.060CI=Confidence Interval; *p-value was derived using log rank test. Citation Format: Saverno K, Cuyun Carter G, Dufour R, Price G, Li L, DeLuca A, Nash Smyth E, Battiato L, Gable J, Walker MS, Huang Y-J, Hannas S, Schwartzberg LS. Outcomes among metastatic breast cancer patients with characteristics that confer a less favorable prognosis [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 P2-08-66.