Comparative Effectiveness of nab-Paclitaxel Plus Gemcitabine vs FOLFIRINOX in Metastatic Pancreatic Cancer: A Retrospective Nationwide Chart Review in the United States.

INTRODUCTION: nab-Paclitaxel plus gemcitabine (nab-P + G) and FOLFIRINOX (FFX) are among the most common first-line (1L) therapies for metastatic adenocarcinoma of the pancreas (MPAC), but real-world data on their comparative effectiveness are limited. METHODS: This retrospective cohort study compared the efficacy and safety of 1L nab-P + G versus FFX, overall and under specific treatment sequences. Medical records were reviewed by 215 US physicians who provided information on MPAC patients who initiated 1L therapy with nab-P + G or FFX between April 1, 2015 and December 31, 2015. Study outcomes were overall survival (OS) and tolerability. OS was compared using Kaplan-Meier curves and adjusted Cox proportional hazards models. RESULTS: In total, 654 medical records were reviewed, including those of 337 and 317 patients initiated on nab-P + G and FFX as 1L MPAC therapy, respectively. nab-P + G-initiated patients were older, less likely to have ECOG ≤ 1, and had more comorbidities than FFX-initiated patients. Median OS (mOS) was 12.1 and 13.8 months for nab-P + G- and FFX-initiated patients, respectively (HR = 0.99, P = 0.96). Among patients with ECOG ≤ 1, mOS was 14.1 and 13.7 months, respectively (HR = 1.00, P = 0.99). Among patients with 1L nab-P + G and FFX, 36.1% and 41.3% received 2L therapy and experienced mOS of 16.3 and 16.6 months, respectively (HR = 1.04, P = 0.76). The rates of diarrhea, fatigue, mucositis, and nausea and vomiting were significantly higher in the FFX than nab-P + G cohort. CONCLUSION: The real-world survival was similar between patients receiving 1L nab-P + G or FFX both overall and among patients who received active 2L treatments. In addition, nab-P + G was associated with significantly lower rates of common AEs compared with FFX. FUNDING: Celgene.

Clinical Outcomes with First-Line Chemotherapy in a Large Retrospective Study of Patients with Metastatic Pancreatic Cancer Treated in a US Community Oncology Setting.

BACKGROUND: The combination chemotherapy regimens of nab-paclitaxel plus gemcitabine (nab-p + G) and FOLFIRINOX (FFX) have each demonstrated improved survival compared with gemcitabine monotherapy in clinical trials for metastatic pancreatic cancer; however, limited comparative data exist. OBJECTIVE: The objective of this study was to compare patient characteristics and clinical outcomes including time to treatment failure and overall survival in patients with metastatic pancreatic cancer receiving first-line chemotherapy in the community. METHODS: We conducted a retrospective, multi-site, observational cohort study of patients with metastatic pancreatic cancer receiving first-line nab-p + G, FFX, or gemcitabine monotherapy between April 2013 and October 2015, using data from the iKnowMed electronic health record database. Patients on clinical trials or with other cancer diagnoses were excluded. Time to treatment failure and overall survival were assessed by Kaplan-Meier methods. RESULTS: Four hundred and eighty-six patients met selection criteria, 255 nab-p + G, 159 FFX, and 72 gemcitabine patients. Median age was 61, 68, and 73 years for FFX, nab-p + G, and gemcitabine patients, respectively (p < 0.01 for nab-p + G vs. FFX). Eastern Cooperative Oncology Group performance status of 0-1 was 91% for FFX, 77% for nab-p + G, and 68% for gemcitabine patients (p < 0.01 for nab-p + G vs. FFX). For the nab-p + G vs. FFX cohorts, respectively, time to treatment failure was 3.7 vs. 4.3 months (log-rank p = 0.25); and OS was 9.8 vs. 11.4 months (log-rank p = 0.38). Among patients with Eastern Cooperative Oncology Group performance status 0-1, time to treatment failure was 4.2 vs. 4.3 months (log-rank p = 0.47); and overall survival was 12.1 vs 11.4 months (log-rank p = 0.68). CONCLUSIONS: The nab-p + G patients were older and had worse performance status than FFX patients. Time to treatment failure and overall survival were not observed to be significantly different in first-line nab-p + G and FFX patients. Results were similar after stratifying by performance status.

Comparative effectiveness of early-line nab-paclitaxel vs. paclitaxel in patients with metastatic breast cancer: a US community-based real-world analysis.

BACKGROUND: Real-world analyses of treatments for patients with metastatic breast cancer are limited. We evaluated the comparative effectiveness of nab-paclitaxel vs. paclitaxel in patients with metastatic breast cancer using data from an electronic medical record database from community practices across the USA. METHODS: We performed a retrospective cohort study using fully de-identified data from an independent US electronic medical record platform of patients with metastatic breast cancer initiating single-agent nab-paclitaxel or paclitaxel as a first- or second-line treatment from December 1, 2010 to October 6, 2014. The clinical efficacy objectives were time to treatment discontinuation (TTD) and time to next treatment (TTNT). Subgroup analyses were performed in patients with 2 types of metastatic breast cancer as follows: 1) hormone receptor-positive and human epidermal growth factor receptor 2 negative, and 2) triple-negative disease. RESULTS: This analysis included 925 patients. Patients receiving nab-paclitaxel vs. paclitaxel had significantly longer TTD (median 4.2 vs. 2.8 months, P<0.0001) and TTNT (median 6.0 vs. 4.2 months, P<0.0001); similar outcomes were observed for patients with hormone receptor-positive/human epidermal growth factor receptor 2 negative disease. Compared with paclitaxel, nab-paclitaxel was associated with significantly longer TTD in patients with triple-negative disease. nab-Paclitaxel was associated with significantly less all-grade neuropathy, anemia, pain, and diarrhea than paclitaxel. Antiemetic and antihistamine use were significantly less frequent with nab-paclitaxel vs. paclitaxel, whereas use of granulocyte colony-stimulating factor, hydrating agents, and bone-directed therapy to decrease skeletal-related events were more frequent. CONCLUSION: nab-Paclitaxel demonstrated improved clinical effectiveness compared with paclitaxel when examining TTD and TTNT in patients with metastatic breast cancer in a real-world setting.

Outcomes research examining treatments, quality of life and costs in HER2-negative and triple-negative metastatic breast cancer: a systematic literature review.

AIM: With the aggregation of real-world data in healthcare, opportunities for outcomes research are growing. In this study, we summarize published literature examining comparative effectiveness research (CER), treatment patterns, quality of life (QoL) and costs in HER2-negative and triple-negative (TN) metastatic breast cancer (mBC). METHODS: PubMed (2010-January 2016) and four conferences (2013-January 2016) were searched using MeSH/keywords, including mBC, QoL, morbidity and therapeutics. Studies relating to CER, treatment patterns, QoL, costs or treatment appropriateness in US patients with HER2-negative/TN mBC were included in the review. RESULTS: Of 1782 identified records, 33 studies met full inclusion criteria: seven related to CER, 18 to treatment patterns, one to treatment appropriateness/navigation, two to QoL and five to costs. Studies varied in objectives, designs and outcomes. Study designs included retrospective chart reviews (52%), retrospective secondary database analyses (27%), economic models (12%), physician surveys (6%) and patient surveys (3%). 25 studies reported results on HER2-negative mBC, six on TN mBC and two on both subtypes. The most common end points examined were treatment patterns, overall survival and progression-free survival. CONCLUSION: Outcomes research in HER2-negative mBC in the USA was limited, specifically among TN patients, indicating an opportunity for further research in this high unmet need population. Endpoints and treatment options varied, thus, it is difficult to draw summary conclusions about these studies. Outcomes research examining real-world data in mBC has increased in recent years, and may continue to grow with the implementation of new policy programs.

Comparison of treatment patterns and economic outcomes among metastatic pancreatic cancer patients initiated on nab-paclitaxel plus gemcitabine versus FOLFIRINOX.

BACKGROUND: The economic burden of metastatic pancreatic cancer (mPC) is substantial while treatment options are limited. Little is known about the treatment patterns and healthcare costs among mPC patients who initiated first-line gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-P + G) and FOLFIRINOX. METHODS: The MarketScan® claims databases were used to identify adults with ≥2 claims for pancreatic cancer, 1 claim for a secondary malignancy, completed ≥1 cycle of nab-P + G or FOLFIRINOX during 4/1/2013 and 3/31/2015, and had continuous plan enrollment for ≥6 months pre- and 3 months after the first-line treatment. Duration of therapy, per patient per month (PPPM) costs of total healthcare, mPC-related treatment, and supportive care were measured during first-line therapy. RESULTS: 550 mPC patients met selection criteria (nab-P + G, n = 294; FOLFIRINOX, n = 256). There was no difference in duration of therapy (p = 0.60) between nab-P + G and FOLFIRINOX. Compared with FOLFIRINOX, patients with nab-P + G had higher chemotherapy drug costs but lower treatment administration costs and supportive care costs (all p < 0.01). CONCLUSIONS: Patients treated with nab-P + G (vs FOLFIRINOX) had similar treatment duration but lower costs of outpatient prescriptions, treatment administration and supportive care. Lower supportive care costs in the nab-P + G cohort were mainly driven by lower utilization of pegfilgrastim and anti-emetics.

Comparative effectiveness and resource utilization of nab-paclitaxel plus gemcitabine vs FOLFIRINOX or gemcitabine for the first-line treatment of metastatic pancreatic adenocarcinoma in a US community setting.

INTRODUCTION: Despite a clinically relevant, statistically significant survival benefit with nab-paclitaxel plus gemcitabine and FOLFIRINOX vs single-agent gemcitabine for metastatic pancreatic cancer (mPC), little is known regarding their real-world effectiveness. We analyzed patients with mPC using a nationally representative electronic medical records database to address this unmet need. METHODS: This retrospective analysis of the Navigating Cancer database compared outcomes among patients who received first-line nab-paclitaxel plus gemcitabine, FOLFIRINOX, or gemcitabine for mPC. Effectiveness, safety, and supportive care use were examined. nab-Paclitaxel plus gemcitabine was the reference for statistical comparisons. RESULTS: Baseline characteristics were similar except age (oldest patients were in the gemcitabine cohort followed by nab-paclitaxel plus gemcitabine, then FOLFIRINOX). Patients receiving nab-paclitaxel plus gemcitabine (n=122) demonstrated similar time to treatment discontinuation (TTD; median, 3.4 vs 3.8 months; P=0.947) and database persistence (DP; median, 8.6 vs 8.6 months; P=0.534) vs FOLFIRINOX (n=80); however, TTD (median, 3.4 vs 2.2 months; P<0.001) and DP (median, 8.6 vs 5.3 months; P=0.030) were significantly longer with nab-paclitaxel plus gemcitabine vs gemcitabine (n=46). There were more any-grade adverse events with FOLFIRINOX or gemcitabine vs nab-paclitaxel plus gemcitabine (95% or 89% vs 84%, respectively). CONCLUSION: This real-world analysis confirms the phase III MPACT trial findings and demonstrates that nab-paclitaxel plus gemcitabine has effectiveness similar to that of FOLFIRINOX but greater tolerability for treating mPC despite younger patients being in the FOLFIRINOX cohort. These findings support nab-paclitaxel plus gemcitabine as an appropriate first-line treatment option for patients with mPC.

Comparison of treatment patterns, resource utilization, and cost of care in patients with metastatic pancreatic cancer treated with first-line nab-paclitaxel plus gemcitabine or FOLFIRINOX.

BACKGROUND: We compared real-world treatment patterns, resource utilization, and cost of care for patients with metastatic pancreatic cancer treated with first-line nab-paclitaxel + gemcitabine or FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, oxaliplatin). METHODS: This was a retrospective study of inpatient and hospital-based outpatient data in the United States. Primary endpoints included median time to treatment discontinuation (TTD) and total cost of care per patient per month. Secondary endpoints included supportive care costs and hospitalization rate and length. RESULTS: Overall, 345 patients were included (nab-paclitaxel + gemcitabine, n = 182; FOLFIRINOX, n = 163). Median TTD was significantly longer with nab-paclitaxel + gemcitabine vs FOLFIRINOX (4.3 vs 2.8 months; P = .0009). Mean acquisition cost was higher with nab-paclitaxel + gemcitabine ($10,643 vs $6549; P = .0043), but mean total cost of care was lower ($16,628 vs $19,936; P = .1740). Supportive care cost was significantly lower with nab-paclitaxel + gemcitabine ($1995 vs $6456; P < .0001). Hospitalization rate and length were both significantly lower with nab-paclitaxel + gemcitabine. CONCLUSIONS: Despite higher acquisition costs with nab-paclitaxel + gemcitabine, FOLFIRINOX-treated patients had higher total costs driven by supportive care. Toxicity-related costs and drug acquisition costs should be considered when evaluating total cost of care.

Health technology assessment on cervical cancer screening, 2000-2014.

OBJECTIVES: The aim of this study was to conduct a review of health technology assessments (HTAs) in cervical cancer screening to highlight the most common metrics HTA agencies use to evaluate and recommend cervical cancer screening technologies. METHODS: The Center for Reviews and Dissemination (CRD), MedLine, and national HTA agency databases were searched using keywords ("cervical cancer screening" OR "cervical cancer" OR "cervical screening") and "HTA" from January 2000 to October 2014. Non-English language reports without English summaries, non-HTA reports, HTAs unrelated to a screening intervention and HTAs without sufficient summaries available online were excluded. We used various National Institute for Health and Care Excellence (NICE) methods to extract key assessment criteria and to determine whether a change in screening practice was recommended. RESULTS: One hundred and ten unique HTA reports were identified; forty-four HTAs from seventeen countries met inclusion criteria. All reports evaluated technologies for use among women. Ten cervical screening technologies were identified either as an intervention or a comparator. The most common outcome metric evaluated was diagnostic accuracy, followed by economic effectiveness. Additional outcome metrics such as the use of adjunct testing, screening intervals, and age-specific testing were commonly evaluated. Nearly one-third (fifteen of forty-four) of HTAs recommended a change in practice. CONCLUSIONS: This review highlights popular metrics used in HTAs for cervical cancer screening. Clinical and economic effectiveness metrics have been consistently assessed in HTAs, while the use of adjunct testing, screening intervals, and age-specific screening became increasingly prevalent from after 2007. Moreover, we observed an increase in optimized recommendations after 2007.

The budget impact of controlling wastage with smaller vials: A data driven model of session sizes in Bangladesh, India (Uttar Pradesh),Mozambique, and Uganda.

INTRODUCTION: Open vial vaccine wastage in multi-dose vials is a major contributor to vaccine wastage. Although switching from 10-dose vials to 5-dose vials could reduce wastage, a higher total cost could be triggered because smaller vials cost more to purchase and store. METHODS: This study drew field data of daily session sizes in local vaccination facilities from Bangladesh, India (Uttar Pradesh), Mozambique, and Uganda, and used Akaike Information Criteria to determine the best fit statistical distribution across various clinic types. These distributions were input to estimate the vaccine wastage using Lee's (2010) model. Inactivated polio vaccine (IPV) immunization was simulated to compare the costs over ten years with 10-dose vials versus 5-dose vials. RESULTS: By switching from 10- to 5-dose vials, the observed open vial wastage rate due to vial size preference and session size for IPV was reduced from 0.25 to 0.11 in Bangladesh, 0.17 to 0.08 in India (Uttar Pradesh), 0.13 to 0.06 in Mozambique, and 0.09 to 0.04 in Uganda, respectively. The cost savings realized from lower IPV wastage did not offset the higher costs of procurement and storage costs associated with smaller dose presentation. CONCLUSION: While our model showed that switching from 10-dose vials to 5-dose vials of IPV reduced open vial wastage, it was not cost-saving.

Comparison of luminescence ADP production assay and radiometric scintillation proximity assay for Cdc7 kinase.

Several assay technologies have been successfully adapted and used in HTS to screen for protein kinase inhibitors; however, emerging comparative analysis studies report very low hit overlap between the different technologies, which challenges the working assumption that hit identification is not dependent on the assay method of choice. To help address this issue, we performed two screens on the cancer target, Cdc7-Dbf4 heterodimeric protein kinase, using a direct assay detection method measuring [(33)P]-phosphate incorporation into the substrate and an indirect method measuring residual ADP production using luminescence. We conducted the two screens under similar conditions, where in one, we measured [(33)P]-phosphate incorporation using scintillation proximity assay (SPA), and in the other, we detected luminescence signal of the ATP-dependent luciferase after regenerating ATP from residual ADP (LUM). Surprisingly, little or no correlation were observed between the positives identified by the two methods; at a threshold of 30% inhibition, 25 positives were identified in the LUM screen whereas the SPA screen only identified two positives, Tannic acid and Gentian violet, with Tannic acid being common to both. We tested 20 out of the 25 positive compounds in secondary confirmatory study and confirmed 12 compounds including Tannic acid as Cdc7-Dbf4 kinase inhibitors. Gentian violet, which was only positive in the SPA screen, inhibited luminescence detection and categorized as a false positive. This report demonstrates the strong impact in detection format on the success of a screening campaign and the importance of carefully designed confirmatory assays to eliminate those compounds that target the detection part of the assay.