Cardiovascular Safety of SGLT2 Inhibitors Compared to DPP4 Inhibitors and Sulfonylureas as the Second-Line of Therapy in T2DM Using Large, Real-World Clinical Data in Korea

457 Background: Benefit of IO (PD1 and PD-L1 inhibitors) for mUC was observed in clinical trials but real-world evidence for benefit and clinical outcomes is limited. Methods: This was a retrospective study of adult pts with mUC who initiated IO regardless of PD-L1 expression in the first- (1L cohort) or second-line (2L cohort) setting between 5/1/2016-1/31/2019 in the US Oncology Network (USON), a network of community oncology practices. Descriptive and Kaplan-Meier analyses to evaluate baseline characteristics, treatment patterns and clinical outcomes were conducted using data from USON’s electronic heath record. Results: Among 393 pts in the 1L cohort, median (range) age at IO initiation was 77 (42, 90+), 74% were male, 69% were White, and 19.1% and 4.1% had ECOG performance status (PS) 2 and 3/4, respectively. Among the 366 pts in the 2L cohort, median (range) age at IO initiation was 70 (29, 90+), 74% were male, 71% were White, and 19.7% and 1.4% had ECOG PS 2 and 3, respectively. Median (range) follow-up durations from IO initiation were 4.2 (0, 34.1; 1L cohort) and 4.1 (0, 31.3; 2L cohort) months (mo), during which time 43.1% (1L cohort) and 44.4% (2L cohort) of pts died. Median overall survival (OS) from IO initiation (95% confidence interval [CI]) was 10.6 (9.7, 13.2) mo for the 1L cohort and 9.4 (7.1, 11.5) mo for the 2L cohort; 1-year survival probabilities (95% CI) were 46.6% (40.1%, 52.8%; 1L cohort) and 43.4% (36.8%, 49.8%; 2L cohort). By the end of the follow-up, 48.1% of 1L pts and 47.8% of 2L pts were alive and did not advance to next line of therapy, and 13.5% of 1L and 13.4% of 2L cohort pts advanced to the next line of therapy. Median (95% CI) treatment durations were 2.6 (2.1, 2.9) and 2.8 (2.2, 3.5) mo for the 1L and 2L cohorts, respectively; 6-mo ongoing treatment probabilities (95% CI) were 26.6% (22.2%, 31.2%; 1L cohort) and 31.4% (26.4%, 36.4%; 2L cohort). Conclusions: OS of pts in the real world receiving 1L and 2L IO appears consistent with clinical trial results, although survival follow-up is limited. A minority of pts received post-IO therapy. Future research should examine influence of pt characteristics and PD-L1 expression on treatment choice and outcomes.

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POS0223 PATTERNS OF JANUS KINASE INHIBITOR CYCLING FOR THE MANAGEMENT OF RHEUMATOID ARTHRITIS IN REAL-WORLD CLINICAL PRACTICE: AN ANALYSIS OF THE OPAL DATASET

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2256 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 330-331

Author(s):

S. Ciciriello ◽

T. Smith ◽

C. Osullivan ◽

K. Tymms ◽

P. Youssef ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Medical Record ◽

Clinical Data ◽

Real World ◽

Visual Analytics ◽

Clinical Care ◽

Janus Kinase ◽

Second Line ◽

First Line ◽

Third Line

Background:There are currently eleven biologic and targeted synthetic (b/ts)DMARDs acting via five different modes of action available for the treatment of RA in Australia. The cost of b/tsDMARDs is subsidized by government for patients that have active RA despite six months of combination csDMARD therapy. Once a patient is eligible, the clinician can prescribe the b/tsDMARD they deem to be the most clinically appropriate for the patient. In Oct 2015 the first JAK inhibitor (JAKi) became available in Australia (tofacitinib, TOF), baricitinib (BARI) became available in Sept 2018, and upadacitinib (UPA) in May 2020. Each of these oral tsDMARDs possess different selectivity profiles towards different members of the JAK family (JAK1–3 and Tyk2).Objectives:The aim of this analysis was to determine the patterns of JAKi cycling in real-world practice in Australia.Methods:Deidentified clinical data were sourced from the OPAL dataset, which is collected in a custom-built electronic medical record during the routine consultation1. Data from patients >18 years with RA who commenced a b/tsDMARD between Jan-2007 and Dec-2020 were included in the analysis. A visual analytics software program was used to display data on medication initiation and cessation dates, and reasons for stopping tsDMARDs, which is recorded in the medical record at the time of the decision.Results:At Dec 2020, 28% of the 52,190 patients with RA in the OPAL dataset were prescribed b/tsDMARDs. Of these patients, 3,850 (26.3%) were currently prescribed a JAKi with 51.4% receiving TOF, 29.2% BARI and 19.4% UPA. In 2020, JAKi initiations accounted for 48.8% of all initiations and 30.7% of 1st line initiations; an increase of 6.1% and 3.5% from 2019, respectively. The percentage of patients switching from a first line JAKi to a second line JAKi rather than an agent with another mode of action increased from 33.1% in 2019 to 42.6% in 2020. This is despite 26.2% in 2019 and 45.8% in 2020 of the patients switching to another JAKi citing lack of efficacy as the reason for JAKi discontinuation. In the period between May 2020, when a third JAKi (UPA) become available, and Dec 2020, the majority of patients switching from first line TOF or BARI to another JAKI switched to UPA (69.4% and 83.9%, respectively), whilst 30.6% of first line TOF patients switched to BARI (30.6%), and 16.1% of first line BARI patients switched to TOF in second line. The majority of patients switching from second line TOF or BARI to a third line JAKi switched to UPA (73% and 96%, respectively), with 27% of second line TOF patients switching to BARI and a very low number moving from second line BARI to TOF (4%). JAKi choice after a third line TOF or BARI was almost exclusively UPA (86.2% and 95.5%, respectively).Conclusion:There has been significant and sustained uptake of JAKi for the management of RA in Australia and JAKi cycling is increasingly common in routine clinical care. Clinical outcomes and persistence following JAKi cycling requires further investigation.References:[1]Littlejohn GO, Tymms KE, Smith T, Griffiths HT. Using big data from real-world Australian rheumatology encounters to enhance clinical care and research. Clin Exp Rheumatol. Sep-Oct 2020;38(5):874-880.Figure 1.Patterns of JAKi cycling for the management of rheumatoid arthritis in first, second and third line switching.Acknowledgements:The authors acknowledge the members of OPAL Rheumatology Ltd and their patients for providing clinical data for this study, and Software4Specialists Pty Ltd for providing the Audit4 platformDisclosure of Interests:Sabina Ciciriello: None declared, Tegan Smith: None declared, Catherine OSullivan: None declared, Kathleen Tymms: None declared, Peter Youssef: None declared, David Mathers: None declared, Claire Deakin: None declared, Hedley Griffiths Consultant of: AbbVie, Gilead, Novartis and Lilly., Geoff Littlejohn Speakers bureau: Over the last 5 years Geoffrey Littlejohn has received educational grants and consulting fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Gilead, Novartis, Pfizer, Janssen, Sandoz, Sanofi and Seqirus.

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Retreatment Patterns and Outcomes Among Patients with Relapsed Multiple Myeloma

Blood ◽

10.1182/blood.v128.22.5935.5935 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5935-5935

Author(s):

Lincy S Lal ◽

Benjamin J Chastek ◽

Cori Blauer-Peterson ◽

Eric M Maiese

Keyword(s):

Multiple Myeloma ◽

Real World ◽

Index Date ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Risk Of Death ◽

Line Therapy ◽

Line Of Therapy

Abstract Introduction: Clinical trials have suggested that retreatment with multiple myeloma (MM) therapy provides clinical benefit (Mohty 2012), however, little is known about real-world utilization and outcomes of retreatment. Information from this analysis will help to better understand the real-world impact of retreatment for management of first MM relapse. Methods: A retrospective claims analysis of commercial and Medicare Advantage patients aged 18 years in the Optum Research Database. To be included, patients had to have ≥ 2 medical claims ≥ 30 days apart with an MM diagnoses (ICD-9 =203.00) between 01 Jan 2009 and 31 Dec 2013 (study period); ≥ 2 lines of therapy and no evidence of hematopoietic cell transplant during the study period and data available for 1 year prior to index date and ≥ 6 months post index date. The date of the first claim of an NCCN recommended MM treatment during the study period was considered the index date. All MM treatments identified < 30 days of the index date were considered part of first line of therapy. An algorithm was developed for identifying subsequent lines of therapy. A new line of therapy was identified when there was a switch to a new agent < 180 days of discontinuation of the prior line of therapy or retreatment with the same treatment ≥ 180 days of discontinuation with previously used agents. Additionally, patients had to be treated for relapse MM defined according to lines of therapy when 1) there was an active line of therapy ≥ 60 days long and there was a gap of ≥ 180 days from the end of the line of active therapy to the start of the next line of active therapy or 2) there was a line of therapy ≥ 180 days long and a different treatment was started, with or without a 180-day gap between discontinuation of the prior line and start of the subsequent line of therapy . The data evaluated in the analysis included baseline demographics, Quan-Charlson comorbidity scores, line of therapy, and clinical outcomes, including treatment duration and overall survival. Data were analyzed using chi-square and t-tests to compare patients with retreatment vs. treatment with a different regimen for first relapse MM (i.e. second-line therapy). Results: A total of 252 patients (mean age: 70 yrs; 48% male) were identified as having second-line treatment for relapse MM; 90 patients (35.7%) were retreated with the same regimen and 162 (64.3%) patients were treated with a different regimen. Mean Quan-Charlson comorbidity scores were equal between the two groups (p=0.585). Among the retreatment group, 48.2% were treated with monotherapy for first-line, compared to 25.2% of the different regimen group (p-value < 0.001). Dexamethasone (dex) monotherapy, bortezomib plus dex, and lenalidomide plus dex were common regimens used in retreatment, see Figure 1. Lenalidomide plus dex was also commonly used as a different regimen for second-line treatment. Additionally, dex monotherapy was significantly less likely to be used as a new therapy compared to being used as retreatment for second-line therapy (p<0.05). Conversely, bortezomib plus lenalidomide plus dex was significantly more likely to be used as a new therapy compared to being used as retreatment for second-line treatment (p<0.05). The mean length of relapse line was 161 days in the retreatment group versus 212 days in the different regimen group (p-value 0.067). The incidence rate of death was 13 events (1.43 events per 10,000 person-days of follow-up) in the retreatment group versus 22 events (1.51 events per 10,000) in the different regimen group (p=0.895). Figure 1: Second-line Treatment Regimens among Patients who Received the Same Regimen (Retreatment) vs. a Different Regimen for the Treatment of First-Relapse MM\s Conclusions: In this analysis, approximately one-third of patients were retreated with the same treatments in first-line and second-line of therapy. Patients who were retreated with the same regimen tended to have shorter duration of second-line therapy. However, risk of death did not appear to differ between the two groups. This real-world analysis suggests that retreatment in second-line may affect the time to next treatment, but may not negatively impact the overall risk of death. Reference: Mohty B, El-Cheikh J, Yakoub-Agha I, et al. Treatment strategies in relapsed and refractory multiple myeloma: a focus on drug sequencing and 'retreatment' approaches in the era of novel agents. Leukemia 2012; 26: 73-85. Figure 1 Figure 1. Disclosures Lal: Optum: Employment. Chastek:Optum: Employment. Blauer-Peterson:Optum: Employment. Maiese:Janssen Scientific Affairs, LLC: Employment.

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Treatment Patterns and Health Care Costs in Commercially Insured Patients with Follicular Lymphoma

Journal of Health Economics and Outcomes Research ◽

10.36469/jheor.2020.16784 ◽

2020 ◽

Vol 7 (2) ◽

pp. 265-276

Author(s):

Nathan Fowler ◽

Guifang Chen ◽

Stephen Lim ◽

Stephanie Manson ◽

Qiufei Ma ◽

...

Keyword(s):

Health Care ◽

Follicular Lymphoma ◽

Health Care Costs ◽

Real World ◽

Economic Burden ◽

Second Line ◽

First Line ◽

Line Therapy ◽

Line Of Therapy ◽

Care Costs

Background: Few studies have estimated the real-world economic burden such as all-cause and follicular lymphoma-related costs and health care resource utilization (HCRU) in patients with follicular lymphoma (FL). Objectives: This study evaluated outcomes in patients who were newly initiated with FL indicated regimens by line of therapy with real-world data. Methods: A retrospective study was conducted among patients with FL from MarketScan® databases between January 1, 2010 and December 31, 2013. Patients were selected if they were ≥18 years old when initiated on a FL indicated therapy, had at least 1 FL-related diagnosis, ≥1 FL commonly prescribed systemic anti-cancer therapy after diagnosis, and did not use any FL indicated regimen in the 24 months prior to the first agent. These patients were followed up at least 48 months and the outcomes, including the distribution of regimens by line of therapy, the treatment duration by line of therapy, all-cause and FL-related costs, and HCRU by line of therapy were evaluated. Results: This study identified 598 patients who initiated FL indicated treatment. The average follow-up time was approximately 5.7 years. Of these patients, 50.2% (n=300) were female, with a mean age of 60.7 years (SD=13.1 years) when initiating their treatment with FL indicated regimens. Overall, 598 (100%) patients received first-line therapy, 180 (43.6%) received second-line therapy, 51 received third-line therapy, 21 received fourth-line therapy, and 10 received fifth-line therapy. Duration of treatment by each line of therapy was 370 days, 392 days, 162 days, 148 days, and 88 days, respectively. The most common first-line regimens received by patients were rituximab (n=201, 33.6%), R-CHOP (combination of rituximab, cyclophosphamide, doxorubicin hydrochloride [hydroxydaunomycin]; n=143, 24.0%), BR (combination of bendamustine and rituximab; n=143, 24.0%), and R-CVP (combination of rituximab, cyclophosphamide, vincristine, and prednisone; n=71, 11.9%). The most common second-line treatment regimens were (N=180): rituximab (n=78, 43.3%) and BR (n=41, 22.8%). Annualized all-cause health care costs per patient ranged from US$97 141 (SD: US$144 730) for first-line to US$424 758 (SD: US$715 028) for fifth-line therapy. Conclusions: The primary regimens used across treatment lines conform to those recommended by the National Comprehensive Cancer Network clinical practice guidelines. The economic burden for patients with FL is high and grows with subsequent lines of therapy.

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A multicenter retrospective study to evaluate real-world clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) and brain metastasis treated with ipilimumab and nivolumab.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.637 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 637-637

Author(s):

Landon Carter Brown ◽

Kunal Desai ◽

Chester Kao ◽

Emily Noelle Kinsey ◽

Patrick Healy ◽

...

Keyword(s):

Brain Metastasis ◽

Brain Metastases ◽

Real World ◽

Objective Response ◽

Cleveland Clinic ◽

Second Line ◽

Exact Test ◽

Predictors Of Response ◽

Best Response ◽

Line Of Therapy

637 Background: The combination of ipilimumab & nivolumab (I+N) followed by maintenance nivolumab has improved outcomes in patients (pts) with mRCC. Little is known about the outcomes in mRCC pts with brain metastasis. In this multicenter retrospective analysis, we present a real-world experience in pts with brain metastasis treated with I+N. Methods: Pts with mRCC and brain metastases treated with I+N at the Duke Cancer Institute and Cleveland Clinic were identified. Pt characteristics were summarized with descriptive statistics. Fisher’s exact test was used to determine predictors of response (alpha 0.05). Results: From 10/2017 to 2/2019, 17 pts received I+N for mRCC with brain metastases. Median age was 60; 29% were female. IMDC risk was 18%/59%/24% favorable/intermediate/poor, and 77% were clear cell histology. Pts received I+N as either first-line (65%) or ≥ second-line (35%) therapy. Of the pts evaluable for response: objective response rate (ORR) was 42% [0% CR]; with 29% achieving stable disease and 18% progressive disease as their best response. Median duration on therapy was 13 weeks. 59% of pts developed an immune-related adverse event (AE). The most common reason for treatment discontinuation was disease progression (47%) followed by AEs (18%). There were no significant predictors of any radiographic response category (PR, SD, or PD) among variables assessed (gender, IMDC risk, histology, presence of bone metastasis, line of therapy, or presence of irAE). Of note, 50% (3/6) patients treated in the second-line or greater setting experienced a PR. Conclusions: In our real-world cohort of mRCC patients with brain metastasis, I+N is clinically effective. Further investigation is warranted in this population given exclusion from prior clinical trials.

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Italian Real-World Analysis of a Tyrosine Kinase Inhibitor Administration as First- or Second-Line of Therapy in Patients with Chronic Myeloid Leukemia

Therapeutics and Clinical Risk Management ◽

10.2147/tcrm.s309342 ◽

2021 ◽

Vol Volume 17 ◽

pp. 617-622

Author(s):

Valentina Perrone ◽

Elisa Giacomini ◽

Margherita Andretta ◽

Loredana Arenare ◽

Maria Rosaria Cillo ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitor ◽

Real World ◽

Myeloid Leukemia ◽

Kinase Inhibitor ◽

Second Line ◽

Line Of Therapy

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Generalizability of Cardiovascular Safety Trials on SGLT2 Inhibitors to the Real World: Implications for Clinical Practice

Advances in Therapy ◽

10.1007/s12325-019-01043-z ◽

2019 ◽

Vol 36 (10) ◽

pp. 2895-2909 ◽

Cited By ~ 5

Author(s):

Antonio Nicolucci ◽

Riccardo Candido ◽

Domenico Cucinotta ◽

Giusi Graziano ◽

Alberto Rocca ◽

...

Keyword(s):

Clinical Practice ◽

Real World ◽

Sglt2 Inhibitors ◽

Cardiovascular Safety ◽

The Real

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An algorithmic approach to deriving line of therapy in a real-world data set for non-small cell lung cancer (NSCLC).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e18099 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e18099-e18099

Author(s):

Chhaya Shadra ◽

James Lin Chen ◽

Cheryl D. Cho-Phan ◽

Aradhana Ghosh ◽

Jonathan Hirsch

Keyword(s):

Metastatic Disease ◽

Real World ◽

Second Line ◽

First Line ◽

Real World Data ◽

Data Set ◽

Algorithmic Approach ◽

World Data ◽

Continuation Therapy ◽

Line Of Therapy

e18099 Background: Real World Data (RWD) is being used for outcomes research and regulatory submissions. A key variable needed to understand treatment outcomes is Line of Therapy (LoT). However, LoT is generally not captured in RWD sources such as electronic health records (EHR) or claims data, and is typically derived using manual abstraction. To determine whether an automated approach to LoT derivation is possible, we created an algorithm and applied it to patients (pts) in the Syapse Learning Health Network. Methods: We selected confirmed NSCLC pts from 4 health systems in the RWD set, verifying diagnosis using ICD-9/10/O3 topography and morphology codes. We analyzed the EHR-derived medication list using a regimen-independent algorithm that classified antineoplastic drugs (AD), as defined by ATC L01, into LoT. Within each LoT, we compared the top 80% of AD prescribed (by volume of pts) to the LoT as indicated on each drug’s FDA label. We then used descriptive statistical summaries to outline the alignment between automated algorithmic results and indicated usage within that LoT. Results: In a set of 10,842 NSCLC pts, a total of 106 unique AD were prescribed in the first line as identified by our algorithm, and 13 drugs were prescribed as first line for 80% of the pts. Of those, 9 (69%) of those are indicated for first line, 3 are not indicated for NSCLC, and 1 is indicated for a subsequent NSCLC line, per FDA labels. 82 unique AD were prescribed in the second line as identified by our algorithm, and 15 drugs were prescribed as second line for 80% of the pts. Of those, 11 (73%) are indicated for treatment/continuation therapy for recurrent, advanced or metastatic disease, 3 are not indicated for NSCLC, and 1 is indicated for first line NSCLC per FDA labels. 36 unique AD were prescribed in subsequent line as identified by our algorithm, and 18 drugs were prescribed as subsequent line for 80% of the pts. Of those, 12 (67%) are indicated for treatment of recurrent, advanced or metastatic disease or subsequent systemic therapy, 5 are not indicated for NSCLC and 1 is indicated for first line per FDA labels. Conclusions: An automated algorithmic approach for deriving lines of therapy may be a viable solution to scalably calculate LoT in RWD sets. A deeper analysis using statistical sensitivity and specificity assessment of such algorithms is needed to validate the potential of an algorithmic approach.

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Real-world outcomes of metastatic urothelial carcinoma (mUC) patients (pts) treated with first or second-line immunotherapies (IO) in the United States (US).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e16025 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e16025-e16025

Author(s):

Marley Boyd ◽

Srinivas Annavarapu ◽

Gurjyot K. Doshi ◽

Kentaro Imai ◽

Eric Sbar ◽

...

Keyword(s):

Clinical Outcomes ◽

Real World ◽

Performance Status ◽

The United States ◽

Current Treatment ◽

Future Research ◽

Second Line ◽

Ecog Performance Status ◽

Using Data ◽

Line Of Therapy

e16025 Background: While clinical trials have affirmed benefit of IO for mUC, limited real-world evidence exists to describe the current treatment landscape and clinical outcomes. This study evaluated these trends in a network of community oncology practices, the US Oncology Network (USON). Methods: This was a retrospective study of adult mUC pts who initiated IO regardless of PD-L1 expression in the first- (1L cohort) or second-line (2L cohort) setting between 5/1/2016-1/31/2018. Using data from USON’s electronic heath record, descriptive and Kaplan-Meier analyses were conducted to evaluate baseline characteristics, treatment patterns and clinical outcomes. Results: Among the 254 pts in the 1L cohort, median (range) age at IO initiation was 74 (42, 90+), 71% were male, 77% were Caucasian, and 18.1% and 5.9% had ECOG performance status (PS) 2 and 3/4, respectively. Among the 179 pts in the 2L cohort, median (range) age at IO initiation was 71 (29, 90+), 76% were male, 76% were Caucasian and 20.7% and 2.2% had ECOG PS 2 and 3/4, respectively. Nearly all pts received IO monotherapy. Median (range) follow-up durations from IO initiation were 4.3 (0, 22; 1L cohort) and 3.6 (0, 19; 2L cohort) months (mo), during which time 39% (1L cohort) and 37% (2L cohort) of pts died. Median overall survival (95% confidence interval [CI]) was 9.9 (7.5, 15.7) mo for the 1L IO cohort and 8.3 (6.4, not reached) mo for the 2L IO cohort. Six-mo survival probabilities (95% CI) were 61.6% (54.5%, 67.9%; 1L cohort) and 60.7% (51.4%, 68.8%; 2L cohort). In total, 52.8% of 1L pts and 53.6% of 2L pts were alive and did not advance to next line of therapy, and 11% of 1L and 13% of 2L cohort pts advanced to the next line of therapy. Median (95% CI) treatment durations were 2.3 (1.9, 3.0) and 3.3 (2.7, 3.9) mos for the 1L and 2L cohorts, respectively. Six-mo ongoing treatment probabilities (95% CI) were 28.9% (23.3%, 34.7%; 1L cohort) and 34.0% (26.1%, 42.1%; 2L cohort). Conclusions: Outcomes of real-world mUC pts receiving IO were as expected, with majority of pts alive and a small minority receiving post-IO therapy. Future research should examine how pt and tumor (PD-L1 expression) characteristics influence treatment and outcomes.

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