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.

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ance in the pre-treatment covariates, reduces bias and reduces variance and deserves consideration in outcomes research studies.

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.

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