Evaluation of Progression-Free Survival as a Surrogate Endpoint for Overall Survival in Metastatic Breast Cancer: Systematic Review and Trial Level Meta-Analysis

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steps in the MCDA approach: defining the problem; identifying the decision makers; establishing the alternatives; selecting an appropriate evaluation method; assigning criteria weights; fixing thresholds; conducting sensitivity analyses; and making a recommendation. The alternatives consisted of cetuximab and bevacizumab combined with either FOLFOX or FOLFIRI chemotherapy. The evaluation method used is ELECTRE 1S, an MCDA application developed for selecting the best alternative from a given set of alternatives.  Results: The outputs generated include each of the following: performance matrix, concordance matrix, discordance matrix, outranking matrix, robustness matrix, primary outranking graph, and final outranking graph. The selection procedure suggested that FOLFOX plus cetuximab was the optimal antibody chemotherapy combination for first-line therapy of patients with KRAS wild- type mCRC. Interestingly, the National Comprehensive Cancer Network in their recently updated colon cancer guidelines (version 2.2015) made similar recommendations.  Conclusions: This study offers a novel procedure for integrated assessment and selection of optimal cancer therapy using a MCDA approach. The evaluation method utilized in this study is both practical and adequate for selection problems. Further investigation of MCDA is desirable. PCN203 Evaluation of Progression-Free Survival as a Surrogate Endpoint for Overall Survival in Metastatic Breast Cancer: Systematic Review and Trial Level Meta-Analysis Adunlin G1, Dranitsaris G2 1Virginia Commonwealth University, Richmond, VA, USA, 2Augmentium Pharma Consulting Inc., Toronto, ON, Canada

Objectives: To assess the statistical validity of using progression-free survival (PFS) as a surrogate endpoint for overall survival (OS) in metastatic breast cancer (mBC) patients receiving 1st, 2nd and beyond 2nd line chemotherapy, alone or in combination with targeted therapies. Methods: A systematic literature search of randomized controlled trials of mBC evaluating anthracyclines, taxanes and targeted therapies reported between January 1, 1990 and August 1, 2015 was performed. Non-parametric Spearman Rank Correlation Coefficient and Weighted Fixed Effects Regression Analysis were used to test the strength of the association between hazard ratios for PFS (HRPFS) and OS (HROS) as well as Δ PFS and Δ OS.  Results: Seventy-two RCTs providing 84 comparative arms met the inclusion criteria. The Spearman Rank correlation coefficient suggested a modest association between HROS and HRPFS (Spearman’s rho =  0.46; p <  0.001) as well as Δ PFS and Δ OS (Spearman’s rho =  0.52; p <  0.001). The weighted multivariable regression modelling indicated that HRPFS was a significant predictor of HROS (model coefficient =  0.18, p =  0.04). However, only 31% (i.e. model R2) of the variability between the PFS-OS association was accounted for. When trials were limited to ≥ 2nd line setting, the strength of the association improved (α  =  0.40, p <  0.001) and R2 increased to 55%. However, the HRPFS - HROS association was no longer significant when only 1stline trials were considered (α  =  0.90).  Conclusions: Improvements in PFS are correlated with increased OS. However, the effect appears to be driven by trials in the ≥  2nd line setting. Therefore, PFS can be a suitable surrogate for OS in mBC trials evaluating new treatments in the 2nd setting and beyond. However, the findings do not support the use of PFS alone as a primary endpoint of trials evaluating new drugs in the 1st line setting. PCN204 Long-Term Disease Outcomes in Symptomatic Multiple Myeloma Patients: A Retrospective Analysis of the Pharos Registry Verelst SG1, Blommestein HM2, De Groot S3, Gonzalez-McQuire S4, DeCosta L5, de Raad J6, Sonneveld P1, Uyl-de Groot CA7 1Erasmus University Medical Center, Rotterdam, The Netherlands, 2Institute of Health Policy & Management, Erasmus University Rotterdam, Rotterdam; Comprehensive Cancer Organisation, Utrecht; Institute for Medical Technology Assessment, Erasmus University Rotterdam, Rotterdam, The Netherlands, 3Institute of Health Policy & Management, Erasmus University Rotterdam, Rotterdam; Institute for Medical Technology Assessment, Erasmus University Rotterdam, Rotterdam, The Netherlands, 4Amgen (Europe) GmbH, Zug, Switzerland, 5Amgen Ltd., Uxbridge, UK, 6Amgen B.V.; University of Utrecht, Breda, The Netherlands, 7Erasmus University Rotterdam, Rotterdam, The Netherlands

Objectives: Data on real-world outcomes and healthcare resource utilisation (HRU) in multiple myeloma (MM) in Europe is limited. This study aimed to provide insights into real-world outcomes (i.e. PFS and OS) and HRU of MM patients in The Netherlands using data from the PHAROS-registry.  Methods: MM patients starting first-, second- or third-line therapy ≥ 2008 were selected from the PHAROS-registry. Note that not all patients in the analysis on second- and third-line were included in the analysis on previous lines (e.g. a patient could have started second-line therapy ≥ 2008, while having started first-line therapy < 2008). The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS) and HRU.  Results: First-line thalidomide-based regimens were prescribed to 66% of patients (n= 608) and bortezomib-based regimens to 15% (n= 139). 19% (n= 170) received another first-line regimen. Median OS (95% confidence interval [CI]) in first- (n= 917), second- (n= 583) and third-line (n= 283) were 37.5(34.8–41.8), 19.7(17.2–22.9) and 13.9(10.5–16.6) months, respectively. Median PFS (95% CI) were 18.0(16.3–18.9), 8.9(7.9–9.7) and 6.4(5.5–7.2) months, respectively. Large differences were seen between subgroups in all treatment-lines, e.g. median OS from first-line therapy ranged from 31.9(29.1-35.4) to 64.6(53.2-not reached) months for patients > 65 and patients ≤ 65, respectively, and was 32.2(29.2-35.5) for patients without prior stem cell transplantation (SCT) (median OS not reached for patients with prior SCT). Similarly, median PFS from first-line therapy ranged from 16.2(14.5-17.9) to 22.6(19.826.5) months for patients > 65 and patients ≤ 65, respectively, and from 15.2(13.6-17.0) to 32.0(26.2-36.5) for patients without or with prior SCT, respectively. Mean (standard deviation [SD]) number of inpatient days per month were 1.7(3.4), 1.4(3.2) and 2.3(4.6) in first, second and third-line, respectively.  Conclusions: In patients receiving first-line therapy for MM between 2008 and 2012 in The Netherlands, median OS was approximately three years. Large differences were observed between subgroups.

PCN205 Evaluating “Value” in Metastatic Colorectal Cancer Treatments: Trends in the Evidence Wang EC1, Yu J1, Chang J1, Sarnes E2, Shields K2 Healthcare Pharmaceuticals, Whippany, NJ, USA, 2Xcenda, LLC, Palm Harbor, FL, USA

1Bayer

Objectives: Leading medical professional societies (eg, ASCO, ESMO, NCCN) have recently released frameworks to facilitate discussions on the value of cancer therapies. This literature review summarizes recent trends on the concept of evaluating value in cancer care, using mCRC as an example.  Methods: Relevant publications were identified using predetermined search criteria in Medline (01/01/200512/31/2015) and abstracts presented at key conferences (01/01/2015- 12/31/2015). Publications were reviewed if they addressed the following topics: providers/prescriber oncology value frameworks, factors influential for payer/reimbursement decision making in oncology, and components of “value assessment” in oncology.  Results: From 13,914 unique results, 322 described mCRC-related pharmacotherapies; 90 met the inclusion criteria (46 in Europe and 39 in US; some covered > 1 country). Value evaluations published as journal articles increased more steadily across the review timeframe in Europe: 23% in 2005-2008, 29% in 2009-2012, and 49% in 2013-2015, while US-based articles were more concentrated in recent years (84% in 2011-2015). The majority of all publications were economic models (62%; primarily cost-effectiveness analyses) followed by retrospective database studies (22%). The publication types varied by country; the majority of European publications were economic models (76%), while US publications were split between database studies (44%) and models (44%). Overall, many of the recent (2010-2015) publications evaluated the value of monoclonal antibodies (mAbs) in mCRC (35 of 65). Of the mAb publications, 71% (25/35) were models and 63% (22/35) were in the first-line setting.  Conclusions: Despite the substantial amount of publications, many focused on cost-effectiveness of mCRC therapies in the first-line setting. Costeffectiveness is only one component of “value assessment.” The value frameworks by oncology medical societies and individual payers/health systems include other important factors (eg, disease rarity, quality of life, affordability, disease burden, drug novelty) into the overall value assessment. However, most of these evaluations do not take line-of-therapy into consideration. PCN206 Uptake of TBO-Filgrastim in the Outpatient Setting among Commercially Insured and Medicare Supplemental Populations in the United States Smoyer KE1, Jones CA2, Johnson BH3, Lane PB4 1Envision Pharma Group, Philadelphia, PA, USA, 2Envision Pharma Group, London, UK, 3Truven Health Analytics, Cambridge, MA, USA, 4Envision Pharma Group, Horsham, UK

Objectives: Tbo-filgrastim (TBO-FIL), a granulocyte-colony stimulating factor (G-CSF), has been available in the USA since November 2013, but approved for only one filgrastim (FIL) indication, reduction of severe neutropenia associated with myelosuppressive chemotherapy. TBO-FIL is classified as a biosimilar in Europe, but not in the USA. Our objective was to identify uptake and utilization patterns of TBO-FIL in an outpatient setting among commercially insured and Medicare supplemental populations from first entry into the US market.  Methods: Patients 18 years and older receiving G-CSF were identified in the Truven Health MarketScan® Databases between January 1, 2014 and March 31, 2014 (Q1 2014) and between April 1, 2015 and June 30, 2015 (Q2 2015). Patients were required to have a cancer diagnosis or evidence of chemotherapy during or in the 12 months prior to the calendar quarter in which they were studied. Patients were also required to have continuous enrollment during the calendar quarter of study. G-CSF use was defined as an outpatient claim for pegfilgrastim (PEG), FIL, or TBO-FIL. Demographics were measured at G-CSF receipt.  Results: In Q1 2014, 11,402 patients met the study criteria (mean age 58.6 [SD= 12.6], 66% female). Some received more than one G-CSF; 9,226 (81%) received PEG (75% PEG only), 2,783 (24%) received FIL (18% FIL only), and 86 (1%) received TBO-FIL (< 1% FIL only). In Q2 2015, 7,958 patients met the study criteria (mean age 58.3 [SD= 12.5], 66% female). Of these, 6,385 (80%) received PEG (74% PEG only), 1,784 (22%) received FIL (17% FIL only), and 304 (4%) received TBO-FIL (3% TBO-FIL only).  Conclusions: The percentage of identified G-CSF patients who received TBO-FIL grew from 1% in Q1 2014 to 4% in Q2 2015, but uptake was relatively low. When data become available, future research will include filgrastim-sndz, the first US biosimilar, approved for five of six filgrastim indications. PCN207 Pharmaceutical Utilization During Childhood Cancer Terminal Admissions Russell H1, Leeds H2, Reichert K2, Bernhardt MB2, Hellsten M1 1Baylor College of Medicine, Houston, TX, USA, 2Texas Children’s Hospital, Houston, TX, USA

Objectives: Healthcare costs during terminal admissions in intensive care settings, are known to exceed other inpatient locations. This research explores the contribution of pharmaceuticals to terminal admissions costs for childhood cancer.  Methods: We reviewed clinical and administrative data from the final 3 calendar days of life for inpatient malignancy-related deaths at a tertiary care children’s hospital between January 2011 and June 2015. Pharmaceuticals were grouped into 6 categories: Comfort, Anti-tumor, Anti-microbial, Fluid/Electrolyte/Nutrition (FEN), Supportive, and Other. Statistical comparisons were performed using regression analysis and considered significant if p< 0.05.  Results: 115 patients died in acute care units (n= 34, 30%), intermediate care/bone marrow transplant units (n= 17, 15%), intensive care units (ICU) (n= 58, 50%), or other locations (n= 6, 5%). Acute care patients were most likely to have CNS or solid tumors (74%) and be admitted for palliation (59%). They received an average of 12 different pharmaceuticals in their final 3 days, at a median cost of $640, 12% of total inpatient costs for those days. Utilization measures were significantly higher in other locations: intermediate care patients received an average of 22 pharmaceuticals for median cost of $4,244, 27% of total costs, and ICU patients received an average of 25 pharmaceuticals for median cost of $5,596, 25% of total costs. Costs for comfort medications were similar