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Introduction: Advanced or metastatic non-small cell lung cancer (NSCLC) is associated with significant symptom burden. It is important to understand the impact of these disease-and treatment-related symptoms on patients' daily lives and explore from a patient perspective what constitutes a meaningful change in NSCLC symptoms. Methods: Patient experience of advanced or metastatic NSCLC was explored in this prospective, non-interventional qualitative research study recruiting patients from the United States (US). Interviews were conducted to explore the most important symptoms, daily life impacts, and patients' perspectives of what constitutes meaningful change when considering their current symptoms versus 6-12 months prior, based on the Patient Global Impression of Severity (PGI-S) and Patient Global Impression of Change (PGI-C) items. Results: Between February and April 2022, 19 US-based patients with Stage IV NSCLC were recruited; 95% were female, 63% were White, 79% had been diagnosed >1 year prior, and 63% were receiving targeted therapy. Over half the patients indicated their most important symptoms were fatigue, shortness of breath, and cough. Patient differentiation between whether symptoms were disease- or treatment-related lacked concordance, and often patients were unable to distinguish the two. The most frequently mentioned impacts of these symptoms on patients' daily lives were difficulty walking, sleep disturbance, anxiety/depression, impact on relationships, and difficulty doing daily tasks. Most patients considered a one-point change on the PGI-S or PGI-C to be meaningful based on rating their symptom severity at the time of the interview compared with 6-12 months before the interview. Conclusion: Based on their own symptom experience, patients with advanced or metastatic NSCLC indicated a one-point threshold for meaningful change, whether improvement or worsening. This suggests a one-point change on the PGI-S or PGI-C may be a potential anchor for patient-reported outcome (PRO) endpoints used in clinical trials. It is important to use PRO instruments that capture the symptoms and impacts identified as most important to patients. These findings highlight the importance of using qualitative methods to assess disease-related symptoms, treatment-related side effects, and the impacts on daily life for patients with advanced or metastatic NSCLC, underscoring how qualitative assessments can complement quantitative PRO instruments for evaluating clinical trials. [ABSTRACT FROM AUTHOR]

Aims: To estimate the economic impact of the introduction of gilteritinib for the treatment of relapsed/refractory (R/R) FLT3 mutation-positive (FLT3mut+) acute myeloid leukemia (AML) from a US payer's perspective. Methods: A budget impact model (BIM) was developed to evaluate the 3-year total budgetary impact of treating adults with R/R FLT3mut+ AML eligible for gilteritinib in a hypothetical US health plan. Total costs (drugs/administration, hospitalization, monitoring, adverse events, transfusions, subsequent hematopoietic stem cell transplantation, post-progression, and FLT3 testing) were estimated before and after gilteritinib entry. The budget impact was the total cost difference between the two scenarios. The target population size and cost inputs were based on public data or published literature, drug market share was informed by market research data, and the model included recommended treatments for R/R FLT3mut+ AML per clinical guidelines. Deterministic sensitivity analyses (DSAs) and scenario analyses varying key model inputs and assumptions were conducted to test for robustness. Results: In a hypothetical health plan with 1 million members, 20.9 adults with R/R FLT3mut+ AML were estimated to be eligible for gilteritinib. Of these, it was assumed 30.0% would be treated with gilteritinib in Year 1 following gilteritinib entry, increasing the total plan budget by $663,795 and the per-member-per-month (PMPM) cost by $0.055. In Years 2-3, the market share of gilteritinib increased to 45.0%, increasing the total plan budget impact by $1,078,371 and $1,087,230, and the PMPM cost by $0.090 and $0.091, respectively. The model results remained robust in DSAs and scenario analyses, with the largest impact observed when the projected uptake of gilteritinib was changed. Limitations: The results of this BIM are contingent upon the model's assumptions and inputs. Conclusions: Adding gilteritinib to the formulary for the treatment of adults with R/R FLT3mut+ AML had a minimal budget impact from a US payer's perspective. [ABSTRACT FROM AUTHOR]

Before the advent of targeted therapies, the conventional treatment for R/R FLT3 SP mut+ sp AML was initial induction with salvage chemotherapy (SC) followed by allogeneic hematopoietic stem cell transplantation (HSCT), if eligible [[3]]. However, patients with R/R FLT3 SP mut+ sp AML receiving SC typically experienced poor clinical outcomes, including low response rates and short overall survival (OS; median: 2-6 months) [[1], [5], [7]]. SC (LDAC) in adult patients with AML; this study reported a NNT of 4 for 1-year OS in patients ineligible for intensive chemotherapy [[11]], similar to the NNT of 5 reported here for gilteritinib. Approximately 30% of patients newly diagnosed with acute myeloid leukemia (AML) have FMS-like tyrosine kinase 3 mutations (FLT3 SP mut+ sp ), conferring a negative effect on prognosis with a high likelihood of relapsing or refractory (R/R) disease [[1]]. [Extracted from the article]

Background: Non--small cell lung cancer (NSCLC) causes significant symptom burden, particularly at advanced stages. Objectives: To gain insight into patients' experience of advanced/ metastatic (adv/met) NSCLC and to identify the symptoms and daily life impacts of importance to patients. Methods: Semistructured, qualitative interviews using open-ended questions and lasting 45 to 60 minutes were conducted by telephone/virtual platform with US patients with a confirmed diagnosis of adv/met NSCLC to explore symptomatology and disease impacts on daily life. Results: Overall, 19 patients (aged 28-71 y; 95% female) were interviewed. Most patients were receiving targeted therapy (63%) and were diagnosed with adv/met NSCLC more than 12 months prior (79%). Patients frequently reported 14 symptoms, with the most common being shortness of breath/difficulty breathing (n=16), fatigue (n=16), cough (n=13), and pain (eg, chest, back; n=9). Patients had difficulty distinguishing disease-related symptoms from treatment-related symptoms, particularly cough, fatigue, and shortness of breath/difficulty breathing. Gastrointestinal symptoms (n=9), hair/skin/nail issues (n=4), sensory changes (eg, vision/taste; n=3), and swelling (n=2) were described as treatment-related symptoms. Patients reported impacts on physical functioning (mainly difficulty walking [n=16]), psychological well-being (mainly anxiety/depression [n=16]), and activities of daily living (ADLs; mainly difficulty performing daily tasks [n=13]). Walking and ADLs were impacted by fatigue and shortness of breath, although pain also contributed to difficulty with ADLs. Patients linked coughing to impaired ability to sleep, impacts on ADLs like conversations/laughing, and impacts on psychological well-being. Conclusions: These interviews indicate that patients with adv/met NSCLC are negatively impacted by disease-related and treatment-related symptoms. Understanding the symptoms and impacts most relevant to patients can help inform which patient-reported outcomes reflect treatment benefits in clinical trials and can support treatment decision- making in clinical practice. Funding: GSK provided funding for this research study. [ABSTRACT FROM AUTHOR]

Objectives: To assess real‐world treatment patterns and healthcare resource utilization (HRU) among patients with FLT3–mutated (FLT3mut) and FLT3–wild‐type (FLT3wt) acute myeloid leukemia (AML). Methods: Data were abstracted from medical charts of patients with AML from 10 countries. Patients were grouped based on their FLT3 mutation status, age (18‐64 or ≥65), and whether they were newly diagnosed (ND) or relapsed/refractory (R/R). Results: Charts of 1027 AML patients were included (183 FLT3mut 18‐64 ND; 136 FLT3mut ≥65 ND; 181 FLT3mut R/R; 186 FLT3wt 18‐64 ND; 159 FLT3wt ≥65 ND; 182 FLT3wt R/R). Substantial heterogeneity was observed in treatment patterns for AML. Among ND patients 18‐64, the most common initial treatment was standard‐to‐intermediate dose cytarabine‐based therapies (43.2% for FLT3mut and 55.9% for FLT3wt); among ND patients ≥65, the most common initial treatment was hypomethylating agent‐based therapies (36.0% and 47.2%). Among R/R patients, the most common initial treatment after R/R was best supportive care only (39.8% and 24.7%). HRU was substantial across cohorts during both event‐free and post‐event periods. Conclusions: Treatment patterns of AML were heterogeneous and FLT3mut AML was treated more aggressively than FLT3wt disease. HRU was substantial for all cohorts, particularly after relapse or treatment failure. [ABSTRACT FROM AUTHOR]

BACKGROUND: Patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) and confirmed feline McDonough sarcoma (FMS)-like tyrosine kinase 3 gene mutations ( FLT3 mut+ ) have a poor prognosis and limited effective treatment options. Gilteritinib is the first targeted therapy approved in the United States and Europe for R/R FLT3 mut+ AML with significantly improved efficacy compared with existing treatments. OBJECTIVE: To evaluate gilteritinib against salvage chemotherapy (SC) and best supportive care (BSC) over a lifetime horizon among adult patients with R/R FLT3 mut+ AML from a US third-party payer's perspective. METHODS: The model structure of this cost-effectiveness analysis included a decision tree to stratify patients based on their hematopoietic stem cell transplantation (HSCT) status, followed by 2 separate 3-state partitioned survival models to predict the long-term health status conditional on HSCT status. The ADMIRAL trial data and literature were used to predict probabilities of patients being in different health states until a conservative cure point at year 3. Afterwards, living patients followed the survival outcomes of long-term survivors with AML. Model inputs for utilities, medical resource use, and costs were based on the ADMIRAL trial, published literature, and public sources. All costs were inflated to 2019 US dollars (USD). Total incremental costs (in 2019 USD), life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. Deterministic sensitivity analyses and probabilistic sensitivity analyses were performed. RESULTS: This work was supported by Astellas Pharma, Inc., which was involved in all stages of the research and manuscript development. Garnham, Pandya, and Shah are employees of Astellas and hold stock/stock options. Zeidan consulted and received personal fees/honoraria and research funding from Astellas. Zeidan also has received research funding from Celgene/BMS, Abbvie, Astex, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Trovagene/Cardiff Oncology, Incyte, Takeda, Novartis, Amgen, Aprea, and ADC Therapeutics; has participated in advisory boards; has consulted with and/or received honoraria from AbbVie, Otsuka, Pfizer, Celgene/BMS, Jazz, Incyte, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Daiichi Sankyo, Taiho, Seattle Genetics, BeyondSpring, Cardiff Oncology, Takeda, Ionis, Amgen, Janssen, Syndax, Gilead, Kura, Aprea, Lox Oncology, Genentech, Servier, Jasper, Tyme, and Epizyme; has served on clinical trial committees for Novartis, Abbvie, Geron, Gilead, Kura, Lox Oncology, BioCryst, and Celgene/BMS; and has received travel support for meetings from Pfizer, Novartis, and Cardiff Oncology. Qi and Yang are employees of Analysis Group, Inc., which received consulting fees from Astellas for work on this study. Part of this material was presented at the American Society of Hematology (ASH) Annual Meeting; December 7-10, 2019; Orlando, FL.CONCLUSIONS: Gilteritinib is a cost-effective novel treatment for patients with R/R FLT3 mut+ AML in the United States. DISCLOSURES: This work was supported by Astellas Pharma, Inc., which was involved in all stages of the research and manuscript development. Garnham, Pandya, and Shah are employees of Astellas and hold stock/stock options. Zeidan consulted and received personal fees/honoraria and research funding from Astellas. Zeidan also has received research funding from Celgene/BMS, Abbvie, Astex, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Trovagene/Cardiff Oncology, Incyte, Takeda, Novartis, Amgen, Aprea, and ADC Therapeutics; has participated in advisory boards; has consulted with and/or received honoraria from AbbVie, Otsuka, Pfizer, Celgene/BMS, Jazz, Incyte, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Daiichi Sankyo, Taiho, Seattle Genetics, BeyondSpring, Cardiff Oncology, Takeda, Ionis, Amgen, Janssen, Syndax, Gilead, Kura, Aprea, Lox Oncology, Genentech, Servier, Jasper, Tyme, and Epizyme; has served on clinical trial committees for Novartis, Abbvie, Geron, Gilead, Kura, Lox Oncology, BioCryst, and Celgene/BMS; and has received travel support for meetings from Pfizer, Novartis, and Cardiff Oncology. Qi and Yang are employees of Analysis Group, Inc., which received consulting fees from Astellas for work on this study. Part of this material was presented at the American Society of Hematology (ASH) Annual Meeting; December 7-10, 2019; Orlando, FL.

Aims: To estimate the economic impact of the introduction of gilteritinib for the treatment of relapsed/refractory (R/R) FLT3 mutation-positive ( FLT3 mut+ ) acute myeloid leukemia (AML) from a US payer's perspective., Methods: A budget impact model (BIM) was developed to evaluate the 3-year total budgetary impact of treating adults with R/R FLT3 mut+ AML eligible for gilteritinib in a hypothetical US health plan. Total costs (drugs/administration, hospitalization, monitoring, adverse events, transfusions, subsequent hematopoietic stem cell transplantation, post-progression, and FLT3 testing) were estimated before and after gilteritinib entry. The budget impact was the total cost difference between the two scenarios. The target population size and cost inputs were based on public data or published literature, drug market share was informed by market research data, and the model included recommended treatments for R/R FLT3 mut+ AML per clinical guidelines. Deterministic sensitivity analyses (DSAs) and scenario analyses varying key model inputs and assumptions were conducted to test for robustness., Results: In a hypothetical health plan with 1 million members, 20.9 adults with R/R FLT3 mut+ AML were estimated to be eligible for gilteritinib. Of these, it was assumed 30.0% would be treated with gilteritinib in Year 1 following gilteritinib entry, increasing the total plan budget by $663,795 and the per-member-per-month (PMPM) cost by $0.055. In Years 2-3, the market share of gilteritinib increased to 45.0%, increasing the total plan budget impact by $1,078,371 and $1,087,230, and the PMPM cost by $0.090 and $0.091, respectively. The model results remained robust in DSAs and scenario analyses, with the largest impact observed when the projected uptake of gilteritinib was changed., Limitations: The results of this BIM are contingent upon the model's assumptions and inputs., Conclusions: Adding gilteritinib to the formulary for the treatment of adults with R/R FLT3 mut+ AML had a minimal budget impact from a US payer's perspective.