Treatment patterns among patients with advanced/recurrent endometrial cancer in the United States.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 291-291
Author(s):  
Jinan Liu ◽  
Eric M Maiese ◽  
Bruno Émond ◽  
Marie-Hélène Lafeuille ◽  
Patrick Lefebvre ◽  
...  

291 Background: Among patients (pts) with endometrial cancer (EC), response rates for platinum-based regimens in the first-line (1L) setting range from 40% to 62% in clinical trials. This study describes patient characteristics, treatment patterns, time to next treatment (TTNT), and overall survival (OS) among pts with advanced/recurrent EC treated with a platinum-based regimen in a real-world setting in the US. Methods: This retrospective study used Optum Clinformatics Extended Data Mart de-identified databases from January 1, 2007, to December 31, 2019. Adult pts with advanced/recurrent EC who initiated a 1L platinum-based regimen and subsequently initiated second-line (2L) antineoplastic therapy were identified. Prior to initiation of 1L, a 12-month washout period of continuous enrollment without use of antineoplastic agents (except hormonal agents) was imposed. Kaplan-Meier (KM) rates were used to report TTNT and OS from 2L, third line (3L), and fourth line (4L), separately. Results: A total of 1878 pts with advanced/recurrent EC initiated 2L therapy following a platinum-based regimen in 1L. Among them, 739 (39.4%) pts initiated 3L and 330 (17.6%) initiated 4L or later (4L+) therapy. Median pt age was 68.0 years. More pts received platinum-based regimens (56.4%) in 2L than other options (Table). Few pts (3.3%) received immunotherapy. Among pts receiving 3L, a similar percentage of pts were treated with platinum-based (33.2%) and other chemotherapy regimens (33.8%); few pts received immunotherapy (3.0%). Among pts receiving 4L+, the most frequent treatment option was other chemotherapy (46.1%). Median TTNT was 17.7, 10.6, and 8.4 months for 2L, 3L, and 4L pts, respectively. KM rates of OS following initiation of 2L therapy at 1, 2, 3, and 4 years were 68.4%, 49.6%, 41.3%, and 33.6%, respectively, with a median OS of 23.5 months. Conclusions: Among pts with advanced/recurrent EC treated with platinum-based therapy in 1L, platinum-based regimens remain prevalent treatment choices in later lines of therapy. In this study, immunotherapy was used infrequently in 2L, 3L, and 4L+. The median TTNT decreased in later lines of therapy. This study highlights a critical need for novel, more effective treatment options in later lines of therapy to optimize outcomes among pts with advanced/recurrent EC.[Table: see text]

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18693-e18693
Author(s):  
Eric M. Maiese ◽  
Bruno Émond ◽  
Jinan Liu ◽  
Marie-Hélène Lafeuille ◽  
Patrick Lefebvre ◽  
...  

e18693 Background: Among patients (pts) with endometrial cancer (EC), response rates for platinum-based regimens in the first-line (1L) setting range from 40% to 62% in clinical trials. This study describes patient characteristics, treatment patterns, time to next treatment (TTNT), and overall survival (OS) among pts with advanced/recurrent EC treated with a platinum-based regimen in a real-world setting in the US. Methods: This retrospective study used Optum Clinformatics Extended Data Mart de-identified databases from January 1, 2007, to December 31, 2019. Adult pts with advanced/recurrent EC who initiated a 1L platinum-based regimen and subsequently initiated second-line (2L) antineoplastic therapy were identified. Prior to initiation of 1L, a 12-month washout period of continuous enrollment without use of antineoplastic agents (except hormonal agents) was imposed. Kaplan-Meier (KM) rates were used to report TTNT and OS from 2L, third line (3L), and fourth line (4L), separately. Results: A total of 1878 pts with advanced/recurrent EC initiated 2L therapy following a platinum-based regimen in 1L. Among them, 739 (39.4%) pts initiated 3L and 330 (17.6%) initiated 4L or later (4L+) therapy. Median pt age was 68.0 years. More pts received platinum-based regimens (56.4%) in 2L than other options (Table). Few pts (3.3%) received immunotherapy. Among pts receiving 3L, a similar percentage of pts were treated with platinum-based (33.2%) and other chemotherapy regimens (33.8%); few pts received immunotherapy (3.0%). Among pts receiving 4L+, the most frequent treatment option was other chemotherapy (46.1%). Median TTNT was 17.7, 10.6, and 8.4 months for 2L, 3L, and 4L pts, respectively. KM rates of OS following initiation of 2L therapy at 1, 2, 3, and 4 years were 68.4%, 49.6%, 41.3%, and 33.6%, respectively, with a median OS of 23.5 months. Conclusions: Among pts with advanced/recurrent EC treated with platinum-based therapy in 1L, platinum-based regimens remain prevalent treatment choices in later lines of therapy. In this study, immunotherapy was used infrequently in 2L, 3L, and 4L+. The median TTNT decreased in later lines of therapy. This study highlights a critical need for novel, more effective treatment options in later lines of therapy to optimize outcomes among pts with advanced/recurrent EC.[Table: see text]


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5581-5581
Author(s):  
Shelby Corman ◽  
Sneha Kelkar ◽  
Shardul Odak ◽  
Jingchuan Zhang ◽  
Vimalanand S. Prabhu ◽  
...  

5581 Background: Traditional platinum-based systemic chemotherapy continue to be the SOC for aEC in the first line. Phase 2 clinical trials of chemotherapy (GOG 129 series) and some targeted therapies (229 series) for second line advanced endometrial cancer (aEC) have proved disappointing. Recently the treatment landscape for aEC patients has significantly changed with newer targeted therapies focusing on the microsatellite instability (MSI) status of endometrial tumors. The objective of the ECHO study was to describe real-world treatment patterns and outcomes in non-MSI-high or DNA mismatch repair proficient (pMMR) aEC patients in clinical practice in the United States (US) prior to 2019. Methods: The ECHO study is a multicenter, retrospective chart review study in women diagnosed with aEC in the US. Data were obtained from medical records of adult women (≥18 years) diagnosed with advanced or inoperable aEC (stages III or IV) with known MSI status, who had received at least one prior systemic therapy and progressed between July 1, 2016 – June 30, 2019. De-identified patient data extracted by treating oncologists included patient demographics, clinical and treatment characteristics, and clinical outcomes. Kaplan-Meier analyses were performed to estimate real-world progression-free survival (rwPFS) and overall survival (OS). Results: A total of 124 non-MSI-high or pMMR aEC patients who had progression following first line therapy were included in this interim analysis. Average age was 63 years, 62.9% White/Caucasian, 16.9% Hispanic/Latino, and 86% had ECOG ≤1. Metastases were observed in 70% of patients at diagnosis, with the most common metastatic sites being lung (47.6%), liver (32.3%), and distant lymph nodes (29%). As 2nd line therapy, 69% of patients received mono or combination chemotherapy (primarily with doxorubicin), 13% hormonal therapy, and 18% targeted therapy ± chemotherapy. Median duration of 2nd line therapy was 4 months. The majority (86.3%) discontinued 2nd line therapy, with disease progression the most common reason (66.4%). A quarter (26.6%) of patients initiated an additional line of therapy. Median rwPFS from initiation of 2nd line therapy was 5 months (95% confidence interval [CI]: 4-9). Median OS from initiation of 2nd line therapy was 12 months (95%CI: 9-18). Estimated OS rates from initiation of 2nd line therapy at 6, 12, and 24 months were 66%, 47%, and 30%, respectively. Conclusions: In this retrospective, chart review study, patients with non-MSI-high/pMMR aEC in the US who failed at least one systemic therapy had poor prognosis on subsequent therapies. There continues to be a significant unmet need in this group of women. Novel therapies are needed that delay progression and/or improve overall survival and further research is indicated to explore this.


2019 ◽  
Vol 15 (35) ◽  
pp. 4069-4081 ◽  
Author(s):  
Ruchitbhai Shah ◽  
Marc Botteman ◽  
Reginald Waldeck

Aim: We conducted this study to describe nonmetastatic castration-resistant prostate cancer (nmCRPC) patient characteristics and treatment patterns in the US, Europe and Japan. Materials & methods: Descriptive analyses were conducted using the 2015–2017 Ipsos Global Oncology Monitor Database. Results: A total of 2065 (442 in the US, 509 in Europe and 1114 in Japan) patients (median age: 74–80 years; stage III at diagnosis : 38.5%; Eastern Cooperative Oncology Group [ECOG] score ≤1: 79.4%; treated by urologist : 88.4%) were included in the analytic cohort. Luteinizing hormone-releasing hormone agonists and antiandrogens were the most commonly used first regimen treatments. With subsequent nmCRPC regimens their use decreased, while the use of chemotherapy, corticosteroids, androgen synthesis inhibitors and second-generation androgen receptor inhibitors increased. Conclusion: These data represent real-world treatment patterns in nmCRPC.


BMJ Open ◽  
2018 ◽  
Vol 8 (7) ◽  
pp. e019955 ◽  
Author(s):  
Xiaomei Ma ◽  
David P Steensma ◽  
Bart L Scott ◽  
Pavel Kiselev ◽  
Mary M Sugrue ◽  
...  

ObjectivesTreatment patterns for patients with myelodysplastic syndromes (MDS) outside clinical trials are not well described. Our objective was to evaluate treatment patterns and patient characteristics that influence time to disease-modifying therapy in patients with MDS in the USA.Design, participants and outcome measuresPatients with MDS treated with erythropoiesis-stimulating agents (ESAs), iron chelation therapy, lenalidomide (LEN) and the hypomethylating agents (HMAs) azacitidine and decitabine, were retrospectively identified in the GE Centricity Electronic Medical Record database between January 2006 and February 2014; LEN and HMAs were defined as ‘disease-modifying’ therapies. Multivariable Cox regression models were used to ascertain patient characteristics associated with time to disease-modifying therapy.ResultsOf the 5162 patients with MDS, 35.7%, 40.3% and 4.6% received 1, ≥1 and ≥2 therapies, respectively. ESAs were the first-line (72.5%) and only (64.0%) treatment in the majority of patients who received ≥1 therapy. ESA-only patients were older and had more comorbidities, including isolated anaemia. LEN and HMAs were first-line treatment in 12.4% of patients each; 32.7% received LEN or HMAs at any time. The majority of del(5q) patients (77.6%) received ≥1 therapy, most commonly LEN, compared with 40% of patients without del(5q). A shorter time to disease-modifying therapy was significantly associated with absence of comorbidities, diagnosis after February 2008, lower baseline haemoglobin level, age <80 years and male gender (p<0.002 for all).ConclusionsA high proportion of patients diagnosed with MDS in the USA do not receive approved disease-modifying therapies. It is important to improve access to these therapies.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4787-4787 ◽  
Author(s):  
Brandon Arnieri ◽  
Coen Bernaards ◽  
Kenneth Wilhelm ◽  
James Black ◽  
Ceri Hirst ◽  
...  

Abstract Introduction: Approximately 18,960 new cases of CLL and 4,660 deaths from CLL are estimated in the US in 2016, with an overall estimated 5-year survival rate of 82%. Despite this, CLL patients with unfavorable genetic features such as 17p deletion have relatively poor outcomes when treated with conventional chemoimmunotherapy (e.g. fludarabine and cyclophosphamide, or bendamustine plus rituximab); however, several new treatments have been approved by the FDA for the treatment of previously untreated CLL in the past 3 years, including obinutuzumab with chlorambucil and ibrutinib. The aim of this analysis was to assess demographics and treatment patterns in patients with previously untreated CLL since the introduction of new treatment options using a novel oncology electronic health record (EHR) database. Methods: A cohort of CLL patients was selected by identifying patients within Flatiron's real-world oncology database. The Flatiron provider network comprises 230 clinics, 2,000 clinicians, and more than 1 million cancer patients throughout the United States (US). Patients included in the cohort were required to meet the following criteria: ≥2 clinic encounters on different days occurring on or after January 1, 2011; ≥1 medication order for an antineoplastic occurring on or after January 1, 2013; physician documentation of CLL; and, evidence in unstructured documents (ie, information not organized in a pre-existing data model, such as free text from a physician note/lab report) of having been treated specifically for CLL. The latter two criteria were assessed based on technology-enabled abstraction of unstructured data (e.g., pathology reports, clinician notes). Patients who lacked unstructured documents, absence of evidence of first-line treatment, or received CLL treatment at a practice outside of the Flatiron network were excluded. The cohort included patients of all ages treated between 2011 and 2015 from all 50 states of the US. The index date was defined as the date of the patient's CLL treatment initiation. Start of first-line therapy after January 1, 2011, was defined as the first episode of an eligible therapy given after or up to 14 days before the date of the patient's CLL treatment initiation. Line of therapy was the first eligible drug episode plus other eligible drugs given within 28 days. Therapies eligible for inclusion in lines of therapy were systemic treatment, as evidenced by an order or administration of an antineoplastic agent recorded in the EHR; radiotherapy and surgery were not included. For patients with documented transformation of CLL, the abstracted date of transformation ended any active line of therapy, and the patient was not considered eligible for any subsequent CLL lines of therapy. Any treatment that occurred after the date of transformation was not included as a CLL line of therapy (steroids were not included in the definition of CLL lines of therapy). Results: As of June 2016, the cohort consisted of 766 eligible CLL patients with a median age of 71 years, and 64% were male (Table 1). While distribution of first-line therapies initiated in 2011 to 2013 remained relatively constant by year, changes were observed during 2014 and 2015 following the introduction of obinutuzumab and ibrutinib (Figure 1); obinutuzumab monotherapy as first-line therapy increased from 8.2% in 2014 to 14.5% in 2015, and ibrutinib monotherapy or ibrutinib + rituximab increased from 10.5% in 2014 to 13.6% in 2015. Of note, fludarabine containing regimens declined from 19.8% in 2012 to 8.8% in 2015. Decreases were also observed with rituximab monotherapy from 21.0% to 16.2%, bendamustine + rituximab (BR) from 36.1% to 31.6%, and rituximab + fludarabine + cyclophosphamide (RFC) from 11.0% to 8.8%. Factors associated with chlorambucil treatment (as monotherapy or in combination) vs. chemoimmunotherapy included older age (75.9 years vs. 68.7 years and 62.6 years for BR and RFC, respectively) and Rai stage (78.1% of patients treated with chlorambucil had Rai stage 0-I disease vs. 70.1% and 71.7% treated with BR and RFC, respectively). A fifth of patients with 17p deletion were treated with ibrutinib. Updated data inclusive of 2016 treatments will be presented. Conclusion: Using a novel EHR database, the marked change in CLL treatments from 2011 to 2015 shows increased utilization of newer agents. Further follow-up and analysis will contrast treatment patterns beyond RCT data in a real-world setting. Disclosures Arnieri: F. Hoffmann La-Roche Ltd: Employment. Bernaards:F. Hoffmann La-Roche Ltd: Employment. Wilhelm:Roche: Equity Ownership; Genentech: Employment. Black:F. Hoffmann La-Roche Ltd: Employment. Hirst:F. Hoffmann La-Roche Ltd: Employment; AstraZeneca: Other: Previous employment . Taylor:F. Hoffmann La-Roche Ltd: Employment. Lambert:F. Hoffmann La-Roche Ltd: Employment. Green:F. Hoffmann La-Roche Ltd: Employment. Lu:F. Hoffmann La-Roche Ltd: Employment. Humphrey:Genentech, Inc.: Employment.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15144-e15144
Author(s):  
Enko Kiprilov ◽  
Laura Sangaré ◽  
Kimberly Lowe ◽  
Alexandra Christodoulopoulou

e15144 Background: The status of mutations in the rat sarcoma viral oncogene homolog ( RAS) family of genes, which includes Kirsten RAS ( KRAS) and Neuroblastoma RAS ( NRAS) predicts response to anti-EGFR therapies in metastatic colorectal cancer (mCRC) patients. Current treatment guidelines recommend all mCRC patients to receive RAS testing prior to initiating treatment with an anti-EGFR agent. This study sought to establish estimates of RAS testing among mCRC patients in the US prior to initiation of first and third lines of treatment, and to describe median survival by treatment groups. Methods: Data from the Oncology Services Comprehensive Electronic Records (OSCER) 2.0 dataset were utilized. Patients diagnosed with mCRC between January 1, 2011 and July 31, 2017 were eligible. Patients were followed for up to 1 year, or until death, following their mCRC diagnosis. Results: A total of 17,387 mCRC patients were included in the analysis, among which 69% were RAS tested and 31% were never tested. Among the RAS tested patients, 23% were tested prior to their mCRC diagnosis 60% received RAS testing following mCRC diagnosis but prior to first line of treatment, 3% were tested following first line treatment but prior to third line, and the remaining 14% were tested following third line. Demographic variables did not differ between tested and untested groups, overall and by line of treatment. The overall median survival of RAS WT patients was 31.1 months (95% CI: 30.0, 32.4). MCRC patients who were not RAS tested had a lower median survival of 20.7 months (95% CI: 19.1, 22.5). Conclusions: The timing of when patients are being tested varies greatly. While nearly 70% of patients had a RAS test, approximately 30% failed to be tested, identifying a large gap in testing practices. Universal RAS testing provides patients and their physicians with knowledge of their anti-EGFR treatment options and may result in improved survival.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4489-4489 ◽  
Author(s):  
Robert M. Rifkin ◽  
Rafat Abonour ◽  
Brian G.M. Durie ◽  
Cristina J. Gasparetto ◽  
Sundar Jagannath ◽  
...  

Abstract Introduction: Between 2009 and 2015, use of novel therapies (immunomodulating drugs and proteasome inhibitors) in multiple myeloma (MM) increased. Regimens initiated during this time frame may help project near-term future treatment patterns. Connect® MM is the first and largest prospective, observational, US-based, multicenter disease registry designed to characterize treatment patterns and outcomes for patients (pts) with newly diagnosed MM (NDMM). Pts with NDMM were enrolled in 2 sequential cohorts from Sep 2009 to Apr 2016. This noninterventional registry did not prescribe or limit therapy choices. Study sites represented all census regions, with 89% and 11% split between community and academic sites, respectively. This allowed a reasonable generalizability to patterns for the US. Methods: Connect® MM enrollment was initiated in Sep 2009 at 250 community and academic sites. Pts were enrolled within 2 months of diagnosis. Cohort 1 enrolled 1493 NDMM pts from Sep 2009 to Dec 2011, and Cohort 2 enrolled 1518 NDMM pts from Dec 2012 to Apr 2016. Data were collected at a baseline visit and quarterly visits thereafter until death or discontinuation. The current analysis was conducted for the population of treated pts (N=2848) as of May 2016. This study examined recorded treatment choice of first-line regimen, maintenance therapy, and second-line regimen in 6-month intervals. Trends in regimens were graphically represented using "Tepee" plots (Srinivasan, Shankar. Resource Tepee. Patent US 7,495,673 B1. 24 Feb 2009). Briefly, all pts who initiated treatment during each 6-month interval are represented horizontally, with each horizontal line indicating 100% of all treatment used in that period. The regimens are represented by gray shading with wider bands signifying the more frequently used regimens at each time interval. Results: Median follow‐up for all pts was 39.3 months (0.03‐78.4) in Cohort 1 and 15.4 months (0.2-40.1) in Cohort 2. For the treated population, the median age was 67 years (range 24‐94), 58% were male, 83% were white, and 38% of those reporting International Staging System stage had stage III MM. By US geographical region, 329 (11.6%) pts were from the Northeast, 1036 (36.4%) from the Midwest, 1117 (39.2%) from the South, 360 (12.6%) from the West, 4 (0.1%) from Puerto Rico, and 2 missing (0.05%). Most pts (2285; 80.2%) were from community sites, and 397 (13.9%) were from academic sites with the remaining from government sites. A total of 1416 (47.4%) reported an intent to transplant (stem cell transplant [SCT]) at the initiation of therapy. A total of 666 (25.8%) have progressed and entered second line. Tepee plots of treatment patterns for start of induction for those pts with and without SCT intent are provided in Figure 1A and 1B, respectively. The year 2012 does not feature in these induction plots, as this period corresponds to a time when pts were not enrolled-Cohort 1 had been completed and Cohort 2 had not yet opened. The 4 most common induction regimens for SCT intent, from left to right, in order of decreasing frequency of use, were lenalidomide (R), bortezomib (V), dexamethasone (D) combined (RVD); VD; cyclophosphamide plus VD (CyBorD); and RD. The 5 most common induction regimens for those without SCT intent, from left to right, in order of decreasing frequency of use, were VD, RD, RVD, CyBorD, and V. Triplet therapy in first-line induction pts increased in frequency from 2009 to 2014. The 4 most frequent maintenance regimens for those with SCT intent were R monotherapy, V monotherapy, RD, and RVD. The 4 most common maintenance regimens for pts who did not intend to receive SCT were R monotherapy, RD, VD, and V monotherapy. The most prevalent regimens in the second line were VD, RD, V, and RVD. Additional graphs including treatment patterns by age group (≤ 70 vs > 70 years) and maintenance by conduct of first-line SCT will be presented. Conclusions: Our work utilizes Tepee plots to outline induction and maintenance treatment patterns over time, for both SCT and non-SCT intent pts, using the largest, prospective, noninterventional registry study in the US. Triplet therapy use increased in the time period studied, with RVD being the most frequently used triplet for pts with or without SCT intent. The most common maintenance regimens included R as monotherapy or in combination. Disclosures Rifkin: Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen/ONYX: Membership on an entity's Board of Directors or advisory committees. Abonour:Celgene: Membership on an entity's Board of Directors or advisory committees. Durie:Amgen: Consultancy; Janssen: Consultancy; Takeda: Consultancy. Gasparetto:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria. Jagannath:Bristol-Myers Squibb: Consultancy; Celgene: Consultancy; Merck: Consultancy. Terebelo:Celgene: Membership on an entity's Board of Directors or advisory committees. Toomey:Celgene: Consultancy. Kitali:Celgene: Employment, Equity Ownership. Zafar:Celgene: Employment. Srinivasan:Celgene: Employment; Individual Patent: Patents & Royalties: US7,495,673B1 Used for MM-Connect Treatment Patterns Abstract.. Hardin:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18036-e18036
Author(s):  
Andrew J. Klink ◽  
Leslie DeMars ◽  
Joice Huang ◽  
Eric M. Maiese ◽  
Bruce A. Feinberg ◽  
...  

e18036 Background: Following disease progression on or after primary (1L) platinum-based therapy (PBT) for advanced/recurrent (A/R) endometrial cancer (EC), patient (pt) prognosis is poor and no consensus on standard second-line therapy exists. This retrospective analysis aimed to understand real-world (RW) treatment patterns of pts with A/R mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) EC who progressed after 1L PBT. Methods: Physicians in Cardinal Health’s Oncology Provider Extended Network submitted retrospective data by abstracting outpatient electronic medical records of pts who received systemic treatment for A/R EC following PBT from 2016 to 2018. Demographics, clinical characteristics, treatments received, and outcomes were summarized descriptively. Results: This study included 84 pts with A/R dMMR/MSI-H EC (table). The majority of participating physicians were hematologists/medical oncologists (80%) and practiced in the community setting (70%). Median duration of therapy (mDOT) in 1L was 4.9 months (95% CI, 4.47–5.57); 64% of pts discontinued treatment due to therapy completion and 35% due to disease progression. In contrast, mDOT in 2L was 6.2 months (95% CI, 5.40–6.37); 37% of pts discontinued treatment due to therapy completion and 44% due to disease progression. The most common MMR/MSI testing modalities were next-generation sequencing (NGS) only, immunohistochemistry (IHC) only, and polymerase chain reaction (PCR) only (table). Conclusions: RW treatment patterns in pts with A/R dMMR/MSI-H EC show that most will undergo PBT retreatment. However, progression is the main reason for discontinuation during retreatment. An urgent need exists for durable therapies that improve prognosis. Opportunities to improve timely testing of MMR/MSI exist. [Table: see text]


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
V McLaughlin ◽  
R Channick ◽  
K Chin ◽  
P Leary ◽  
C Miller ◽  
...  

Abstract Introduction The OPsumit® Historical USers cohort (OrPHeUS) is a multicentre, US, retrospective medical chart review conducted to supplement the OPsumit® USers (OPUS) Registry to fulfil the FDA request to characterise the safety of macitentan in clinical practice. Purpose To describe patient characteristics, treatment patterns, hepatic safety and survival in patients with pulmonary hypertension (PH) newly treated with macitentan. Methods OrPHeUS (NCT03197688) aimed to include 2200 new users of macitentan, between October 2013 and March 2017, who were not enrolled in OPUS. Here we present patients with follow-up data, including characteristics and treatment patterns at macitentan initiation, hepatic adverse events (HAEs) identified using preferred terms in chart entries and pharmacovigilance reporting, hospitalisations and survival. Results OrPHeUS included 2982 patients newly treated with macitentan and with follow-up data; the reason for macitentan prescription was pulmonary arterial hypertension (PAH) in 2362 (79.3%) patients, other PH aetiologies in 612 (20.6%) patients and 8 patients with other/unknown reasons. At macitentan initiation, the median (Q1, Q3) age of the patients was 62 (51, 72) years and 73.9% were female. WHO functional class (FC) was documented in 654 (21.9%) patients, 35.6% of patients were in FC I/II and 64.4% in FC III/IV; median (Q1, Q3) 6-minute walk distance, documented in 411 (13.8%) patients, was 293 (200, 383) metres. At macitentan initiation, 41.5% (n=1239) of patients were not receiving PAH therapy, 46.3% (n=1382) were already receiving one PAH therapy and 11.9% (n=356) were already receiving two PAH therapies. The median (Q1, Q3) exposure to macitentan was 14.9 (5.6, 27.1) months; 57% and 43% of patients had exposures of >12 and >18 months. During the exposure period, 933 (31.3%) patients discontinued treatment, including 474 (15.9%) patients who discontinued due to an adverse event (AE), 6 (0.2%) due to a HAE, 449 (15.1%) for reasons other than an AE/HAE, and 4 (0.1%) for unknown reasons. There were 275 (9.2%) patients who experienced ≥1 HAE (incidence rate [IR]: 0.07 [95% CI, 0.06, 0.08] per 1 person-year); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3x upper limit of normal (ULN) were experienced by 113 (3.8%) patients (IR: 0.028 [95% CI, 0.023, 0.033] per 1 person-year); ALT/AST ≥x3 ULN and bilirubin ≥2x ULN was experienced by 33 (1.1%) patients (IR: 0.008 [95% CI, 0.006, 0.011] per 1 person-year). There were 1148 (38.5%) patients who experienced at least one hospitalisation (IR: 0.36 [95% CI, 0.34, 0.39] per 1 person-year). The 12-month Kaplan-Meier survival estimate was 92% (95% CI, 91, 93). Conclusion OrPHeUS provides additional real-world evidence in patients newly treated with macitentan, confirming the hepatic safety profile of macitentan. Acknowledgement/Funding Actelion Pharmaceuticals Ltd


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2268-2268
Author(s):  
Joseph Feliciano ◽  
Nate Way ◽  
Gerald Engley ◽  
Nilanjan Ghosh

Abstract Introduction: Treatment of relapsed or refractory classical Hodgkin lymphoma (R/R cHL) in patients considered ineligible for stem cell transplant (SCT) in the United States (US) has evolved since 2011. It is important to understand the current treatment landscape and the outcomes associated with current standards of care as new treatment options have been introduced. This analysis provides recent real-world evidence on patient characteristics, treatment patterns, and outcomes in R/R cHL patients in the US who are initially considered ineligible for SCT and are treated with or without brentuximab vedotin (BV). Methods: Hematologists and oncologists (N=205) from the US retrospectively identified patients diagnosed with R/R cHL who received at least two lines of therapy and received their most recent line of therapy between January 2014 and May 2018. The physicians were responsible for abstracting data and completing response forms for variables of interest. The current analysis focused on patients who were considered ineligible for SCT by their physician: descriptive statistics on patient demographics/clinical characteristics, treatment patterns, and outcomes by line of therapy; bivariate analyses (chi-square) comparing treatment modalities by line of therapy. Results: Physicians retrospectively identified 297 patients that they considered ineligible for SCT. Mean (SD) age at initial cHL diagnosis was 53.0 (18.5), most patients were male (69.4%) and Caucasian (61.3%). The most common cHL subtype at diagnosis was nodular sclerosis HL (40.4%), and patients had either Stage I/II (45.8%) or Stage III/IV (54.2%) cHL at initial diagnosis. Median follow-up time for the cohort included here was 15.96 months from initiation of 1L treatment. The majority of the cohort (N = 297) received systemic therapy alone (84.5%) compared to those who received systemic therapy in combination with radiation therapy (RT) (15.5%) in 1L. 1L systemic regimens included regimens that contained ABVD alone or ABVD in combination with other regimens (69.4%). Of those who used ABVD alone or in combination with another regimen (N = 206), 24.8% used a PET adapted approach and deescalated to AVD (N = 51) and 11% escalated to be BEACOPP (N = 18). Other systemic regimens included AVD (10.1%), BEACOPP (7.4%) and ICE (5.7 %). The majority of patients achieved a complete response (CR) or partial remission (PR) after 1L therapy (41.4%, 38% respectively) while 34.1% (N = 61) failed to achieve remission or progressed while on therapy. The most common systemic regimens in 2L (N = 293) were BV monotherapy or in combination with bendamustine (34.6%), salvage regimens [including ICE, DHAP, ESHAP or gemcitabine based combinations] (33%), re-challenge with a previous 1L regimen (19.5%), and PD-1 inhibitors (10.8%). Very few patients received systemic therapy in combination with RT (6.7%) in 2L.The most common systemic regimens used in 3L (N = 21) for the selected cohort of patients not eligible for SCT were BV monotherapy (28.6%) and PD-1 inhibitors (33.3%). Median (range) number of cycles in 2L and 3L was four (1-18) and two (1-14), respectively. Treatment outcomes were variable for patients in 2L and 3L. In 2L, 27.6% achieved a CR, 25.6% achieved a PR, while 24.2% and 15.8% were refractory or progressed on treatment. There were no CRs reported in 3L (N = 21). 26 patients died in 2L and 3L combined. Conclusion/Summary: Given the rapid evolution of therapies used to treat R/R cHL, these findings fill a crucial data gap in real-world evidence on patient characteristics, treatment patterns, and outcomes of patients deemed SCT ineligible in the US. Disclosures Feliciano: Seattle Genetics: Employment. Way:Kantar Health: Employment; Seattle Genetics: Research Funding. Engley:Seattle Genetics: Employment. Ghosh:Juno: Consultancy, Research Funding; SGN: Consultancy, Research Funding, Speakers Bureau; PCYC: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy; Spectrum: Consultancy; Gilead: Consultancy, Speakers Bureau; Pharmacyclics, an Abbvie Company: Consultancy, Research Funding, Speakers Bureau; Genentech: Research Funding; F. Hoffman-La Roche Ltd: Research Funding; Abbvie: Consultancy, Speakers Bureau; Forty seven Inc: Research Funding; TG Therapeutics: Honoraria, Research Funding.


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