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.

determination. 22 drugs met NICE's EOL-SPP for the indication for which they were being appraised. Twelve of these drugs had the EOL-SPP criterion applied to the only indication for which they were licensed. The EOL-SPP criterion was applied to the cumulative populations of ten drugs which had marketing authorization for more than one indication. The seven drugs that did not meet the EOL-SPP criterion all had individual indications which were within the number of what is considered acceptable (Յ7,000), but had total cumulative populations that were greater. Two STAs in particular stand out. The appraisal committee accepted that panitumumab met the EOL-SPP criterion for its current indication but noted that the EMA recommended a marketing extension which would raise the expected patient population to 10,000. In its final appraisal determination for abiraterone NICE overturned its original decision that the drug did not meet the EOL-SPP criterion, even though it noted that abiraterone may be recommended for a marketing extension for a greater patient population. CONCLUSIONS: There is no evidence to suggest NICE applies the EOL-SPP to the cumulative populations of currently licensed indications plus potential future indications. Estimates of the quality-adjusted life-years (QALYs) gained and incremental cost per QALY gained were then compared the assessments of the Amélioration du Service Médical Rendu (ASMR) made by the Haute Autorité de Santé (HAS) in France for the same drugs in the same clinical indications. RESULTS: In the UK, the estimates of QALYs gained ranged from 0.018 to 1.85 and estimates of incremental cost-per QALY from £1800 to £458,000. The estimate of incremental cost per QALY was a good predictor of the level of restriction imposed on the use of the drug concerned. Patient access schemes, which normally imply price reductions, were proposed in 45% of cases. In France, the distribution of ASMRs was 1, 16%; 2, 8%; 3, 21%; 4, 24%; 5, 24%; and uncategorized/ non-reimbursed, 8%. Since ASMRs of 4 and above signify minor or no improvement over existing therapy, these ratings imply that, in around half the cases, the drugs concerned would face price controls. Overall, the assessments of value added in the two jurisdictions produced very similar results. A superior ASMR rating was a good predictor of both higher QALYs gained and a lower incremental cost per QALY. CONCLUSIONS: We conclude that, despite the contrasting approaches employed in France and the UK for assessing the value added by new drugs, the overall assessments of value added produced very similar results. However, the implications of these assessments for patient access to, and prices of, anticancer drugs in the two jurisdictions require further investigation.

s201were from all regions of the United States (Northeast, 19.3%; North Central, 15.7%; South, 44.7%; West, 16.1%; Puerto Rico/Virgin Islands, 0.4%); approximately 60% of patients were female and the mean (SD) age was 53.6 (12.0) years. Overall, 6.1% of patients were biologic naive, 41.9% received ≥ 1 prior biologic therapy, and 52.0% had missing information about prior biologic use. Among patients with prior biologic use, 38.6% had 1 reported biologic efficacy failure, 33.8% had 2 efficacy failures, and 27.7% had ≥ 3 efficacy failures; the most commonly reported biologic efficacy failures were adalimumab (67.4%) and etanercept (59.1%). For both initial and maintenance dosing, approximately half of patients were prescribed secukinumab 300 mg (51.1% and 51.6%, respectively). ConClusions: In this analysis of SRFs filled by patients with PsA and their health care providers, approximately half of patients were prescribed secukinumab 300 mg for both initial and maintenance dosing. These results provide early insights into the prescribing patterns of secukinumab for PsA in a US real-world setting. Future research is needed to better understand how clinical characteristics and treatment history may affect secukinumab usage in US patients with PsA.