French Retrospective Database Analysis of Patient Characteristics and Treatment Patterns in Patients with R/R FLT3-Mutated AML: A Registry-Based Cohort Study.

INTRODUCTION: There is a dearth of evidence to document treatment of FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML) in real-world settings before the introduction of FLT3 inhibitors. A retrospective cohort study was conducted to understand treatment practices prior to the availability of FLT3 inhibitors in patients with FLT3-mutated AML from two registries in France. METHODS: Patient data from January 1, 2009 to December 31, 2017 were collected from the Hauts-de-France and Midi-Pyrénées registries. Patients aged ≥ 18 years at diagnosis with FLT3-mutated AML were included. Demographic and disease characteristics of patients with FLT3-mutated AML and relapsed or refractory (R/R) FLT3-mutated AML were documented. Treatment regimens, overall survival (OS), and event-free survival were assessed in patients with R/R FLT3-mutated AML who did not participate in clinical trials. RESULTS: Overall, 819 and 1244 adult patients with AML from the Midi-Pyrénées and Hauts-de-France cohorts, respectively, underwent FLT3 mutation testing; 172 (21.0%) and 263 (21.1%) patients, respectively, had a FLT3 mutation. Primary R/R status was identified in 41.3% (n = 71/172) of the Midi-Pyrénées and 34.6% (n = 91/263) of the Hauts-de-France cohorts. Before R/R AML diagnosis, 82.0% and 97.5% of patients in the Midi-Pyrénées and Hauts-de-France cohorts, respectively, achieved complete remission (CR) or CR with incomplete hematologic recovery (CRi) following induction chemotherapy; after diagnosis of R/R AML, CR/CRi rates with salvage therapy were 33.3% and 28.1%, respectively. Median OS (interquartile range) in patients receiving salvage therapy (n = 49, n = 78) was 5.2 (2.3-11.1) and 6.1 (2.5-35.2) months, in the Midi-Pyrénées and Hauts-de-France cohorts, respectively. Across both cohorts, patients with R/R FLT3-mutated AML had low rates of CR/CRi with salvage therapy and a median OS of approximately 6 months. CONCLUSION: Before FLT3 inhibitor availability, real-world treatment patterns and outcomes in French patients with R/R FLT3-mutated AML were consistent with clinical trial data, highlighting a poor prognosis and unmet need for effective treatment.

Acute myeloid leukemia is a cancer affecting the blood and bone marrow. The presence of specific mutations in the FMS-like tyrosine kinase 3 (FLT3) gene in patients with acute myeloid leukemia can negatively impact response to standard chemotherapy. Patients with these mutations may not respond to chemotherapy or have a shortened duration of response causing a return of the disease, which in turn substantially decreases their life span. In the era prior to the availability of drugs specifically designed to counteract the negative effects of FLT3 mutations, evidence related to patient characteristics and treatment effects in individuals with acute myeloid leukemia harboring FLT3 mutations was mainly derived from clinical studies, with little evidence based on real-world experience. To better understand real-world patient characteristics and treatment effects in patients with acute myeloid leukemia and FLT3 mutations, we analyzed patients from two French registries, Midi-Pyrénées and Hauts-de-France, with a focus on patients who did not respond to or whose disease returned after initial chemotherapy. Patient data from between January 2009 and December 2017 included patients with FLT3-mutated acute myeloid leukemia from Midi-Pyrénées and Hauts-de-France who did not respond to or had recurrent disease after responding to initial chemotherapy, had low response to salvage chemotherapy, and a survival duration of 6 months or less. Our real-world observations in patients with relapsed or refractory FLT3-mutated acute myeloid leukemia from these two registries were consistent with results reported in clinical trials. Our results highlight the bleak forecast for these patients in the absence of effective drugs.

Adjuvant treatment patterns and outcomes in patients with stage IB-IIIA non-small cell lung cancer in France, Germany, and the United Kingdom based on the LuCaBIS burden of illness study.

OBJECTIVES: To inform health-technology assessments of new adjuvant treatments, we describe treatment patterns in patients with complete resection of stage IB-IIIA non-small cell lung cancer (NSCLC) in France, Germany, and the United Kingdom (UK). MATERIALS AND METHODS: Data were collected via medical record abstraction. Patients were aged ≥18 years with completely resected stage IB-IIIA NSCLC, diagnosed between 01 January 2009 and 31 December 2011. Median follow-up was 26 months. Adjuvant treatment patterns and clinical outcomes were summarized descriptively. RESULTS: Among the 831 patients studied, 239 (29%) had stage IB disease, 179 (22%) had stage IIA disease, 165 (20%) had stage IIB disease, and 248 (30%) had stage IIIA disease. Adjuvant systemic therapy was received by 402 patients (48.4%), (France, 61.8%; Germany, 51.9%; UK, 33.4%). Use of adjuvant therapy increased with increasing stage of disease. Cisplatin/vinorelbine and carboplatin/vinorelbine were the most frequently prescribed adjuvant regimens. Median disease-free survival was 48.0 months (95% confidence interval [CI] 42.3-not estimable); the 25th percentile was 13.2 months (95% CI, 11.0-15.3). 204 patients (24%) died during the follow-up period. The median overall survival was not reached, the 25th percentile was 31.2 months (95% CI 26.8-36.0 months). 272 patients (33%) had disease recurrence during the follow-up period. For 86 of those patients, the first recurrence was local or regional with no distant metastasis and 14 had further progression to metastatic disease during the follow-up time. For the other 186 patients, the first recurrence involved distant metastases. A total of 200 patients had metastatic disease at any time during study follow-up. CONCLUSIONS: Less than half the patients with stage IB-IIIA NSCLC in this observational study received adjuvant systemic therapy. A high rate of first recurrence with distant metastatic disease was observed, emphasising the need for more effective systemic adjuvant therapies in this population.

Economic burden of resected (stage IB-IIIA) non-small cell lung cancer in France, Germany and the United Kingdom: A retrospective observational study (LuCaBIS).

OBJECTIVES: New adjuvant treatments are being developed for patients with resected non-small cell lung cancer (NSCLC). Due to scarcity of real-world data available for treatment costs and resource utilization, health technology and cost-effectiveness assessments can be limited. We estimated the burden and cost-of-illness associated with completely resected stage IB-IIIA NSCLC in France, Germany and the United Kingdom (UK). MATERIALS AND METHODS: Eligible patients were aged ≥18 years with completely resected stage IB-IIIA NSCLC between August 2009 and July 2012. Patients (living or deceased) were enrolled at clinical sites by a systematic sampling method. Data were obtained from medical records and patient surveys. Direct, indirect and patient out-of-pocket expenses were estimated by multiplying resource use by country-specific unit costs. National annual costs were estimated based on disease prevalence data available from published sources. RESULTS: 39 centers provided data from 831 patients of whom patient surveys were evaluable in 306 patients. Median follow-up was 26 months. The mean total direct costs per patient during follow-up were: €19,057 (France), €14,185 (Germany), and €8377 (UK). The largest cost drivers were associated with therapies received (€12,375 France; €3694 UK), and hospitalization/emergency costs (€7706 Germany). Monthly direct costs per patient were the highest during the distant metastasis/terminal illness phase in France (€15,562) and Germany (€6047) and during the adjuvant treatment period in the UK (€2790). Estimated mean total indirect costs per patient were: €696 (France), €2476 (Germany), and €1414 (UK). Estimates for the annual national direct cost were €478.4 million (France), €574.6 million (Germany) and €325.8 million (UK). CONCLUSION: To our knowledge, this is the first comprehensive study describing the burden of illness for patients with completely resected stage IB-IIIA NSCLC. The economic burden was substantial in all three countries. Treatment of NSCLC is associated with large annual national costs, mainly incurred during disease progression.