Best Supportive Care Research Articles

EE378 Cost-Effectiveness Analysis of a Digital Health Application (DIGA) Plus Best Supportive Care (BSC) Compared to BSC in German Episodic Migraine Patients

EE378 Cost-Effectiveness Analysis of a Digital Health Application (DIGA) Plus Best Supportive Care (BSC) Compared to BSC in German Episodic Migraine Patients

EE432 Budget Impact Analysis of Avelumab + Best Supportive Care (BSC) as First-Line Maintenance Treatment in Patients With Locally Advanced or Metastatic Urothelial Carcinoma (la/mUC) in Ireland

EE432 Budget Impact Analysis of Avelumab + Best Supportive Care (BSC) as First-Line Maintenance Treatment in Patients With Locally Advanced or Metastatic Urothelial Carcinoma (la/mUC) in Ireland

Estimating recurrences prevented and costs avoided with atezolizumab in early non-small cell lung cancer in the United States.

Recurrence of early-stage non-small cell lung cancer (eNSCLC) is associated with significant mortality and costs. Atezolizumab (ATZ) was recently approved as adjuvant treatment following resection and platinum-based chemotherapy for adults with stage II-IIIA NSCLC with PD-L1 expression ≥1% after demonstrating significant improvement in disease-free survival (DFS) relative to best supportive care (BSC) in the IMpower010 trial (NCT02486718). This study evaluated the population-level impact of ATZ as adjuvant treatment for eNSCLC in the United States by estimating the number and costs of recurrences avoided. A Monte Carlo simulation model estimated the cumulative number of recurrences and deaths prevented, along with direct, indirect, and terminal care costs, by treating eNSCLC patients with ATZ compared to BSC. The model included eligible patients treated in any given year and followed over a 5-year period. Recurrence and mortality rates and costs were based on the IMpower010 data and supplemented by estimates from published literature. An estimated 4400 eNSCLC patients in the United States were eligible for adjuvant ATZ in any given year, of whom 2387 would experience recurrence within 5 years with BSC. Following the introduction of ATZ, 1030 (95% confidence interval [CI]: 1023, 1036) recurrences and 369 (95% CI: 362, 376) deaths would be avoided with estimated reductions in cumulative recurrence-related direct, indirect, and terminal care costs of $785million, $15million, and $32million, respectively, over a 5-year time horizon. Adjuvant ATZ is estimated to prevent a significant number of recurrences and reduce the economic burden of eNSCLC.

Longitudinal, Real-World Data Reveal Treatment Effectiveness in Idiopathic Multicentric Castleman Disease and Support Current Treatment Guidelines

Background: Idiopathic multicentric Castleman disease (iMCD) is an immunologic disorder with unknown etiology that is diagnosed in approximately 1200 individuals in the US annually. Presentation is heterogeneous - ranging from mild/moderate constitutional symptoms to severe multi-organ dysfunction. Treatment guidelines were developed by an international expert panel in 2017 based on the review of a limited number of clinical trials and small case series. Siltuximab, a monoclonal antibody against interleukin-6 (IL6) approved for the treatment of iMCD, is recommended first-line based on evidence from its phase II trial. High-dose steroids and cytotoxic chemotherapy are recommended for patients with severe disease who progress on anti-IL6 therapy. For patients with mild/moderate disease not responding to IL6 blockade, rituximab +/- immunomodulators is recommended. While concurrent steroids are recommended in some cases, steroid monotherapy is discouraged. Limited data exist on the effectiveness of these agents beyond siltuximab. Herein, we evaluate treatment regimens administered to a cohort of 83 iMCD patients with longitudinal treatment and response data. Methods: A review of cases in the ACCELERATE natural history registry by a panel of experts led to the identification of 83 patients with confirmed iMCD. Longitudinal treatment and response data were abstracted from medical records. Durable treatment response was defined as the best response according to the change in the proportion of abnormal clinical/laboratory criteria sustained for at least 1 year. Severity at the time of treatment initiation was defined as ≥2 of renal failure, fluid accumulation, severe anemia, pulmonary involvement, or hospitalization. Survival analysis for time-to-next-treatment, a proxy for time to treatment failure, was performed on regimens categorized in the guidelines: siltuximab +/- best supportive care (BSC), tocilizumab +/- BSC, rituximab +/- BSC, chemotherapy +/- other agents, and steroid monotherapy. BSC includes steroids, transfusions, and other supportive modalities. Log rank test was used to determine differences across treatment regimens, and pairwise comparisons were Bonferroni corrected. Results: Approximately half (47%) of the patients were female, with a mean (SD) age at diagnosis of 35.9 (16.2). A total of 261 regimens were administered across the cohort. Of the 41 patients who received siltuximab +/-BSC, 44% (N=18) achieved a durable response. Durable response rates to other treatments included: tocilizumab +/-BSC: 41% (7/17); rituximab +/-BSC: 23% (6/26); chemotherapy +/-BSC: 38% (8/21); steroid monotherapy: 6% (2/32). Steroid monotherapy was significantly less likely to induce a durable response than siltuximab +/-BSC (p=0.02). Notably, response rates were significantly lower across modalities in severe compared to mild/moderate disease (p=0.004). We also found that the treatment regimen significantly predicts time-to-next-treatment (p<0.0001, Figure 1). Median time-to-next-treatment for siltuximab +/-BSC is 742 days (95% CI: 1.26, no upper limit), tocilizumab +/-BSC is 689 days (234, no upper limit), rituximab +/- BSC is 153 days (116, 399), chemotherapy +/- other agents is 463 days (107, 791), and steroid monotherapy is 64 days (36,129). Pairwise comparison demonstrated that siltuximab +/-BSC, tocilizumab +/-BSC, and chemotherapy each have a significantly longer time-to-next-treatment compared with steroids (p<0.05). Further, siltuximab +/- BSC also had a significantly longer time-to-next-treatment than rituximab +/-BSC (p=0.02). There were no other differences between regimens. Discussion: Though guidelines were developed in 2017, this is the first systematic assessment of iMCD treatment regimens included in these guidelines. We found differences in durable response rates and in time-to-next-treatment between regimen approaches. Patients on steroids alone require additional drug-intervention a median of 2 months after treatment start, while patients treated on siltuximab +/-BSC remained on treatment for a median of 2 years before additional interventions were added. Our results support current recommendations to administer siltuximab first-line and limit steroid monotherapy use. These results also demonstrate that additional agents are needed for refractory patients, who have few options and are at risk of death due to progression. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Evolution of the Genetic and Biological Studies Performed at Diagnosis in Patients with Acute Myeloid Leukemia Included in the Pethema Epidemiological Registry (REALMOL Study)

INTRODUCTION Risk-adapted therapies based on cytogenetic and molecular markers are being increasingly complemented by targeted therapies, such as FLT3-TKD, FLT3-ITD, IDH1/2 inhibitors. Together, risk-adapted and targeted strategies may help to improve the clinical outcomes of AML patients. However, although extensive genetic and molecular panel screening is nowadays recommended at diagnosis, these prognostic markers or actionable mutations may not always be available in routine practice, and therefore a proportion of patients will not be screened. As of today, there is little information on evolving diagnostic practices based on epidemiologic registry data. AIMS: The REALMOL study describes main genetic studies performed at diagnosis in adult AML patients included in the PETHEMA AML registry through last 20 years. METHODS We conducted a retrospective study to provide insights into genetic and molecular diagnostic methods performed at diagnosis in routine clinical practice in adult AML (non-APL) patients included in the Spanish PETHEMA Registry (NCT02607059), between 2000 and October 2021. All AML patients with available information on both FLT3-ITD and NPM1 test (performed/not performed) were eligible. The primary endpoint of the study was the percentage of screened patients for genetic (karyotype and Fluorescence in situ hybridization) and molecular analysis (conventional PCR for NPM1 and FLT3-ITD, and next-generation sequencing [NGS]) over time, according to patient characteristics, and the type of AML. RESULTS A total of 7,285 adult AML patients were eligible, 4023 patients were male (55.3%), and median age was 66 years (18-99). Two thirds of patients (n=4816) had de novo AML, and ECOG performance status was <2 in 72%. Therapeutic approach was intensive chemotherapy (IC) in 63%, attenuated therapy (non-IC) in 21%, and best supportive care (BSC) in 16% of patients. Throughout the entire period, karyotype was performed in 91% of patients, Fluorescence in situ hybridization (FISH) in 70.3%, NPM1 in 69.2%, FLT3-ITD in 72.0%, and NGS in 19.9% of patients (Table 1). The percentage of screened patients for all genetic and molecular analyses increased over the different periods (2000-2007, 2008-2016 and 2017-2021) (Table 1). Regarding FLT3-ITD determination, it was 82.6% in 2000-2007 (most were performed retrospectively), 91.8% in 2008-2016, and 95.1% in 2017-2021 (Figure 1). Regarding NGS testing, 0.1% in 2000-2007 (most were performed retrospectively), 3.5% in 2008-2016, and 72% in 2017-2021. Age, type of AML (de novo vs. secondary), ECOG and therapeutic approach (BSC vs. IC or non-IC) also significantly influenced the percentage of genetic and molecular studies performed at diagnosis (Table 1). In a multivariate model including all these variables, therapeutic approach (BSC vs. IC/non-IC) was the most relevant factor for not requesting a karyotype study (O.R.: 6.057, 95%C.I. 4.702-7.802, p<0.0001), followed by ECOG ≥2 vs 0-1 (O.R.: 1.733, 95%C.I. 1.388-2.165, p<0.0001), age at diagnosis ≥70 years vs <70 years (O.R.: 1.520, 95%C.I. 1.184-1.950, p=0.001) and secondary vs. de novo AML (O.R.: 1.279, 95%C.I. 1.031-1.588, p=0.025). Regarding FLT3-ITD, the year of diagnosis (<2017 vs ≥2017) was the most influential factor (95% CI 8.408-14.494, p<0.0001), followed by treatment strategy (BSC vs. IC/non-IC, OR: 2.393, 95% CI 1.994-2.873, p<0.0001), age at diagnosis ≥70 years (OR: 1.766, 95% CI 1.537-2.030, p<0.0001), ECOG ≥2 (OR: 1.285, 95% CI 1.114-1.481, p=0.001) and secondary AML (OR: 1.191, 95% CI 1.037-1.369, p=0.014). The year of diagnosis was also the most important factor in the performance of the NGS study (<2017 vs ≥2017) (or 75.713, 95%CI 60.840-94.221, p<0.0001), followed by treatment with BSC (OR 4.287, 95% CI 2.835-6.483, p=0.000), age <70 years (OR 2.374, 95% CI 1.888-2.985, p=0.000) and ECOG ≥2 (OR: 1.365, 95% CI 1.049-1.776, p=0.020). CONCLUSIONS Our study provides relevant information about the diagnostic use of the main genetic and molecular markers in AML in the real-life. The use of all genetic and molecular analysis increased from 2000 to 2021, reflecting complexity of AML diagnostic needs. Age, type of AML, ECOG and therapeutic approach also influenced the type of diagnostic studies performed. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Application of Newly Developed IPSS-M and Comparison of Different Prognostic Systems in Patients with Myelodysplastic Syndrome

Introduction: A risk-adapted treatment strategy is of crucial importance in patients with myelodysplastic syndromes (MDS). With the rapid development of high through-put technology like next generation sequence (NGS), multiple mutations have been revealed as significant factors in MDS. However, previous risk prognostic scoring systems such as the International Prognostic Scoring System (IPSS), the revised IPSS (IPSS-R), and the World Health Organization-classification-based Prognostic Scoring System (WPSS) did not integrate molecular abnormalities. The newly published IPSS-Molecular (IPSS-M) model, which combining genomic profiling with hematologic and cytogenetic parameters in the IPSS-R system (including bone marrow blasts, platelets and hemoglobin), was recently developed to evaluate the associations with leukemia-free survival (LFS), leukemic transformation, and overall survival (OS). This model is considered to be a valuable tool for clinical decision-making. However, it has not yet been widely validated in the clinic. This study is to further validate the prognostic power of IPSS-M based on the real-world data, and to compare the prognostic value of different scoring systems in patients with MDS. Methods：A population of 255 adult MDS was considered. The IPSS-M Web calculator (https://mds-risk-model.com) was used to calculator a tailored IPSS-M score of each patient, and the risk category was therefore divided correspondingly. We then compared the IPSS-M prognostic power to that of IPSS, IPSS-R, and WPSS. The receiver operating characteristic curve (ROC) was used to evaluate the efficiency of the prognostic models. The Spearman's rank correlation rho was used to evaluate the relevance of different tools. Kaplan-Meier (K-M) survival curve with Log-Rank analysis was performed in the study. Results: Median follow-up was 33.2 (95%CI: 27.8-41.1, reverse K-M) months for the whole cohort. Median OS was 28.3 (21.3-35, K-M) months. We mapped at least one oncogenic gene alteration in 75% of patients with MDS, and found that TET2 (23%), ASXL1 (19%), TP53 (15%), DNMT3A (10%), U2AF1 (9%), SF3B1(9%), EZH2 (9%), RUNX1 (5%), WT1 (5%) and SETBP1(5%) are the top 10 genes with the highest mutation frequency (Fig. 1a). Similar with the other three prognostic systems, IPSS-M risk classification was statistically significant for OS (P<0.0001 for IPSS-M, P=0.00061 for IPSS, P<0.0001 for IPSS-R and WPSS) and LFS (P<0.0001 for IPSS-M, IPSS, IPSS-R and WPSS) (Fig 1b). However, no prognostic tool predicted the probability of achieving an objective response. Among the four risk stratification tools, WPSS was more superior in sensitivity and accuracy for OS, while IPSS-M was more superior for LFS (Fig. 1c). The Spearman's rho of IPSS-M with IPSS, IPSS-R and WPSS was 0.646, 0.786 and 0.729, respectively. This indicated that IPSS-M was more correlated with IPSS-R. The mapping C-index between IPSS-R and IPSS-M categories resulted in improved discrimination across the OS and LFS but not leukemic transformation (Fig. 2a). Additionally, it is also resulted in the re-stratification of 45% of MDS patients (114/255) (Fig. 2b). Of these, 85 (33%) were upstaged and 29 (11%) were down-staged. Among re-stratified patients, 19 of 80 (24%) had one mutated gene in IPSS-M, whereas 23 of 80 (29%) had two or more (Fig. 2c). Thus, patient re-stratification was not a single gene effect, but the cumulative contribution of the prognostic mutations for each patient. To further explore the effect of hypomethylation agents (HMAs) or best supportive care (BSC) on different groups, we analyzed the K-M survival curves of higher-risk (HR) and lower-risk (LR) groups stratified by IPSS-M and IPSS-R (Fig. 2d). The results showed that compared with BSC, HMAs did not improve OS and LFS either in HR or LR groups. In patients treated with HMAs, IPSS-M was more superior in both sensitivity and applicability than IPSS-R in OS, with the C-index value of 0.611 vs. 0.582. Conclusions: Overall all prognostic scoring systems well represent the prognostic risk of MDS patients. A highly significant correlation was found between the IPSS-M and IPSS-R risk classifications. IPSS-M provides relevant information for the implementation of risk-adapted strategies in MDS. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

RTID-06. A RANDOMIZED CONTROLLED TRIAL USING ACCELERATOR-BASED BNCT SYSTEM FOR REFRACTORY RECURRENT HIGH-GRADE MENINGIOMA

Abstract BACKGROUNDS Recently, nuclear reactors have been replaced with accelerator-based neutron sources (ABNS) for boron neutron capture therapy (BNCT). High-grade meningiomas (HGM) are refractory, especially recurred after some radiotherapy. We are now applying randomized controlled trial (RCT) of “A phase II clinical trial using accelerator-based BNCT system for refractory recurrent high-grade meningioma”. STUDY DESIGN PMDA in Japan which is a counter part of FDA in USA suggested the importance of RCT even for this exploratory clinical trial for HGM. Along to this suggestion, we prepared 2 study groups, BNCT test treatment group and control best supportive care (BSC) group. Progression free survival (PFS) was set-up as primary endpoint. Rescue BNCT is allowed for control group patients, if they showed progress disease (PD) during observation. Two-dimensional modified Macdonald criteria is adopted for assessment. METHODS The trial started in August 2019. Eighteen subjects were enrolled and divided in 12 and 6 subjects for BNCT and control BSC group, respectively. Cyclotron-based ABNS system was used for neutron source. Neutron-irradiation time is determined not to exceed to 7.5 Gy-Eq for scalp dose which was referencing preceding phase I trial for malignant gliomas. The last patient-in was August 2021. INTERIM RESULTS (as of April 30, 2022): All 6 cases of control group were judges as PD. Seven out of 11 cases of BNCT group were judged as PD. One case of BNCT group dropped out from the study with withdrawal of consent. Median PFS were 8 and 64 weeks for control group and BNCT group, respectively. Log-rank test showed marked statistical difference with p-value of 0.000401 between these 2 groups. CONCLUSIONS This RCT showed a marked difference of PFS between accelerator-based BNCT group and control group, so far. We will keep on observation at least next 2 years for other endpoints.

137MO Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC): Longer-term follow-up from the Asian subgroup of the JAVELIN Bladder 100 trial

In the JAVELIN Bladder 100 trial (NCT02603432), avelumab (anti–PD-L1) 1L maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) and progression-free survival (PFS) vs BSC alone in patients with advanced UC that had not progressed with 1L platinum-based chemotherapy. Previously reported initial data from patients enrolled in Asia were consistent with data from the overall trial population. Here, we report longer-term efficacy and safety data from the Asian subgroup.

Serum SALL4 as a predictive biomarker for the prognosis of patients with hepatocellular carcinoma who underwent nonsurgical treatment.

To investigate the role of serum spalt like transcription factor 4 (SALL4) in the hepatocellular carcinoma (HCC) patients with nonsurgical treatment. Serum samples were collected from 101 patients with HCC without surgical treatment, then the SALL4 was detected by enzyme linked immunosorbent assay. According to subsequent treatment, patients were divided into 2 groups, best supportive care (BSC) (58 cases) and nonsurgical anticancer treatment (NSAT) (48 cases). Kaplan-Meier survival analysis and Cox multivariate regression analysis were applied to evaluate the relationship between SALL4 and survival time of 2 groups. In BSC group, there was no significant difference of the survival time between 2 groups (SALL4 < 800 ng/mL or SALL4 ≥ 800 ng/mL) (P = .339). In NSAT group, the survival time of patients with low SALL4 concentration was significantly longer than patients with high SALL4 concentration (P = .005). SALL4 have no predictive effect in BSC patients with HCC. But for patients received NSAT, low SALL4 concentration in serum may indicate longer survival.

Impact of centralization of care for malignant peritoneal mesothelioma: A historical cohort study from the Dutch mesothelioma expert centers

BackgroundMalignant peritoneal mesothelioma (MPM) is a rare and aggressive cancer that has a poor prognosis. An earlier population-based study found that the majority of Dutch patients do not receive anti-cancer treatment. In 2015, Dutch Malignant Mesothelioma care was centralized in two expert centers. We reviewed treatment patterns at these centers, to assess the impact of centralization of MPM care in the Netherlands. MethodsData from all patients referred to the Dutch MPM expert centers from 2014 to 2020, were retrospectively collected. Descriptive statistics regarding referrals, patient and tumor characteristics, and treatment patterns were provided. Population-based incidence rates were provided by the Netherlands Cancer Registry. ResultsFrom 2014 to 2020, 78 patients were referred to the Dutch Mesothelioma expert centers, of whom 32 were female (41%). From 2014 to 2017, 27 patients were referred, whereas 51 patients were referred from 2018 to 2020. This represents about 24% and 61% of the estimated population incidence, respectively. Treatment patterns were comparable between both periods. Between 2014 and 2018, 33% of patients underwent surgery, 44% systemic therapy, and 22% received best supportive care (BSC), while this was 29%, 37%, and 33% respectively from 2018 to 2020. ConclusionCentralization of care for patients with MPM resulted in an increase of annual referrals to the Dutch mesothelioma expert centers. While population-based incidence did not change during the study period, the absolute number of patients receiving treatment at our centers did increase. This might be considered a first important step towards better treatment for patients with this fatal disease.

Cost-utility analysis of brigatinib compared to alectinib in the treatment of ALK-positive NSCLC in patients previously not treated with an ALK inhibitor

Objective: The aim of this economic evaluation was to assess the cost-utility of brigatinib versus alectinib in the treatment of naïve patients to anaplastic lymphoma kinase-positive advanced non-small cell lung cancer (ALK-positive aNSCLC) from the perspective of the Italian National Health Service (INHS). Methods: A partitioned survival model with four health states (progression-free [PFS], no central nervous system progression [CNS-PFS], central nervous system progression [CNS-PD] and death) was used. The clinical data (progression-free survival, overall survival and time to progression) was based on the ALTA-1L trial for brigatinib and on ALEX trial for alectinib. Utility values were derived from EORTC QLQ-C30 scores evaluated in the ALTA-1L trial and literature. Costs included frontline therapies, subsequent therapies, best supportive care (BSC), administration, concomitant medications, adverse events and health states. Direct medical costs and benefits (quality-adjusted life-years, QALYs) were discounted at a 3.0% annual rate. Uncertainty was assessed using deterministic (DSA) and probabilistic sensitivity analyses (PSA). Results: The analysis showed that brigatinib was dominant versus alectinib; brigatinib led to a gain of 0.216 QALYs and to a treatment cost reduction of € 85,635. The results of the DSA showed that no parameters of the model significantly modified the base case result. Conclusions: This economic evaluation suggested that, compared with alectinib, brigatinib can be considered a valid cost-utility option from the perspective of INHS in the treatment of patients with ALK-positive aNSCLC.

Addition of Niraparib to Best Supportive Care as Maintenance Treatment in Patients with Advanced Urothelial Carcinoma Whose Disease Did Not Progress After First-line Platinum-based Chemotherapy: The Meet-URO12 Randomized Phase 2 Trial

BackgroundPlatinum-based chemotherapy (PBCT) is the standard first-line treatment for advanced urothelial carcinoma (UC). Potential cross-sensitivity can be hypothesized between platinum drugs and poly-ADP ribose-polymerase (PARP) inhibitors. ObjectiveTo compare maintenance treatment with the PARP inhibitor niraparib plus best supportive care (BSC) versus BSC alone in patients with advanced UC without disease progression after first-line PBCT. Design, setting, and participantsMeet-URO12 is a randomized, multicenter, open-label phase 2 trial. Patients with advanced UC, without disease progression after four to six cycles of PBCT, with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, were enrolled between August 2019 and March 2021. Randomization was stratified by ECOG performance status (0/1) and response to PBCT (objective response/stable disease). InterventionPatients were randomized (2:1) to experimental arm A (niraparib 300 or 200 mg daily according to body weight and baseline platelets, plus BSC) or control arm B (BSC alone). Outcome measurements and statistical analysisThe primary endpoint was progression-free survival (PFS). The analysis was performed on an intention-to-treat basis. The secondary endpoints reported in this primary analysis are progression-free rate at 6 mo and safety (adverse event rate). Results and limitationsFifty-eight patients were randomized (39 in arm A and 19 in arm B). The median age was 69 yr, ECOG performance status was 0 in 66% and 1 in 34%; and the best response with chemotherapy was objective response in 55% and stable disease in 45%. The median PFS was 2.1 mo in arm A and 2.4 mo in arm B (hazard ratio 0.92; 95% confidence interval 0.49–1.75, p = 0.81). The 6-mo progression-free rates were 28.2% and 26.3%, respectively. The most common adverse events with niraparib were anemia (50%, grade [G]3 11%), thrombocytopenia (37%, G3–4 16%), neutropenia (21%, G3 5%), fatigue (32%, G3 16%), constipation (32%, G3 3%), mucositis (13%, G3 3%), and nausea (13%, G3 3%). The main limitation of the study is the small sample size: in March 2021, approval of maintenance avelumab for the same setting rendered randomization of patients in the control arm to BSC alone unethical, and accrual was stopped prematurely. ConclusionsAddition of maintenance niraparib to BSC after first-line PBCT did not demonstrate a significant improvement in PFS in patients with UC. These results do not support the conduction of a phase 3 trial with single agent niraparib in this population. Patient summaryIn this trial, we tested the efficacy of niraparib as maintenance treatment in patients affected by advanced urothelial cancer after the completion of first-line chemotherapy. We could not demonstrate a significant improvement in progression-free survival with maintenance niraparib.

Assessing the Cost-effectiveness of a Hypothetical Disease-modifying Therapy With Limited Duration for the Treatment of Early Symptomatic Alzheimer Disease

PurposeClinical trials have produced promising results for disease-modifying therapies (DMTs) for Alzheimer’s disease (AD); however, the evidence on their potential cost-effectiveness is limited. This study assesses the cost-effectiveness of a hypothetical DMT with a limited treatment duration in AD. MethodsWe developed a Markov state–transition model to estimate the cost-effectiveness of a hypothetical DMT plus best supportive care (BSC) versus BSC alone among Americans living with mild cognitive impairment (MCI) due to AD or mild AD. AD states included MCI due to AD, mild AD, moderate AD, severe AD, and death. A hypothetical DMT was assumed to confer a 30% reduction in progression from MCI and mild AD. The base case annual drug acquisition cost was assumed to be $56,000. Other medical and indirect costs were obtained from published literature or list prices. Utilities for patients and caregivers were obtained from the published literature and varied by AD state and care setting (community care or long-term care). We considered 3 DMT treatment strategies: (1) treatment administered until patients reached severe AD (continuous strategy), (2) treatment administered for a maximum duration of 18 months or when patients reached severe AD (fixed-duration strategy), and (3) 40% of patients discontinuing treatment at 6 months because of amyloid plaque clearance and the remaining patients continuing treatment until 18 months or until they reached severe AD (test-and-discontinue strategy). Incremental cost-effectiveness ratios (ICERs) were calculated as the incremental cost per quality-adjusted life-year (QALY) gained. FindingsFrom the health care sector perspective, continuous treatment with a hypothetical DMT versus BSC resulted in an ICER of $612,354 per QALY gained. The ICER decreased to $157,288 per QALY gained in the fixed-duration strategy, driven by large reductions in treatment costs. With 40% of patients discontinuing treatment at 6 months (test-and-discontinue strategy), the ICER was $125,631 per QALY gained. In sensitivity and scenario analyses, the ICER was the most sensitive to changes in treatment efficacy, treatment cost, and the initial population AD state distribution. From the modified societal perspective, ICERs were 6.3%, 20.4%, and 25.1% lower than those from the health care sector perspective for the continuous, fixed-duration, and test-and-discontinue strategies, respectively. ImplicationsUnder a set of assumptions for annual treatment costs and the magnitude and duration of treatment efficacy, DMTs used for a limited duration may deliver value consistent with accepted US cost-effectiveness thresholds.

AML-085 Real-World Treatment Patterns and Clinical Outcomes in Romanian Patients With AML Unfit for First-Line Intensive Chemotherapy

Acute myeloid leukemia (AML) predominantly affects the elderly, and prognosis declines with age. Induction chemotherapy plus consolidation therapy is the standard of care for fit patients; options for unfit patients include hypomethylating agents (HMA), low dose cytarabine (LDAC), targeted therapies, and best supportive care (BSC). This retrospective chart review evaluated clinical outcomes in unfit Romanian patients with AML who initiated first-line treatment or BSC 01/01/2015-12/31/2018. Overall survival (OS), progression-free survival (PFS), time-to-treatment failure (TTF), and response rates were assessed. Of 98 patients, 84 (85.7%) received systemic therapies: HMA, LDAC, and other therapies; 14 (14.3%) received BSC. Median OS at the time of data collection was 8.6 months, significantly lower in the BSC group (3.4 months) than in those who received an HMA as a first line systemic therapy (FLST) (10.0 months). The most frequent cause of death was AML progression, infection, and other comorbid conditions in the FLST group and AML progression in the BSC group. Median PFS was 6.0 months, significantly longer in those who received an HMA as FLST than in those who received other types of therapies (8.0 months in those who received HMA vs. 6.4 months in LDCA vs. 3.4 in the BSC group). Median TTF was significantly longer in the BSC group (3.6 months) as compared to the systemic therapy group (2.1 months in those who received HMAs, 0.4 months in those who received LDCA, and 1.0 months in those who received other systemic therapies). The best overall response in the FLST group was stable disease in 20.2% of the patients, partial remission (PR), and progressive disease (PD) in 9.5% of the patients, and complete remission (CR) in 8.3% of the patients, with a median time from the start of treatment to the best response of 110.5 days. Our findings highlight the unmet need for novel therapies for unfit patients.

A Retrospective Review of the Clinical Outcomes of Lung Cancer Patients Referred into the Regional Neuro-Oncology Pathway in 2020 in Merseyside, United Kingdom

Abstract AIMS The aim of this project was to review the outcomes of patients referred via our regional neuro-oncology pathway who received neurosurgery, SRS, whole brain radiotherapy (WBRT), chemotherapy (SACT) or best supportive care (BSC). METHOD All lung cancer patients discussed at our Neuro-Oncology MDT in 2020 were identified. Patient characteristics and outcomes were obtained from the regional lung and neuro-oncology MDT notes and electronic case notes from Clatterbridge Cancer Centre. Overall survival (OS) was calculated from the date of diagnostic scan to death. The date of data cut-off was 15/10/2021. RESULTS Full datasets were available for 100 patients discussed at the Neuro-Oncology MDT. 65 were adenocarcinomas, 4 had ALK or EGFR mutations and 49 were synchronously presenting with brain metastases and lung cancer. At data cut-off 84 deaths had occurred. The median OS in days was calculated for surgery (207), SRS (360), surgery and cavity boost (298), SACT (249), WBRT (102) and BSC (60). A grouped comparison of SRS and surgery versus other interventions or best supportive care found a statistically significant advantage favouring SRS or surgery (Median OS 360 days, p=0.001). When comparing the synchronous versus asynchronous setting, the combined median OS of the neurosurgical, SRS or SACT cohorts was 276 versus 170 days but there was no difference in WBRT or BSC. CONCLUSION This real-world data details the number of lung cancer patients referred to and receiving neurosurgery or SRS via the Merseyside neuro-oncology MDT. This data supports pre-existing evidence that those who receive SRS or neurosurgery have a superior OS.

AML-208 Treatment Results in Patients With AML Between 60 and 75 Years of Age: Experience of a Center

Acute myeloid leukemia (AML) patients aged 60 years or older have a 5-year overall survival (OS) of 3%-8%. Assess treatment outcomes in terms of global response (complete response [CR] and CR with incomplete recovery [CRi]) and identify the impact of clinical and therapeutic characteristics on OS. Retrospective cohort study between January 1st, 2010, and May 31st, 2021. Hospital Italiano de Buenos Aires. Patients aged 60-75 years with AML diagnosis. Summary measures were reported as mean and standard deviation or median and interquartile range (IQR). Categorical comparisons were made using the Chi-square test. Survival analysis was performed using Kaplan-Meier, and subgroups were compared using the log-rank test. Cox regression analysis was used for comparative analysis by covariates. Eighty-nine patients were included, and median follow-up was 6.8 months (IQR 1.5-20.1). Of these, 34 (38.2%) received intensive chemotherapy (CMT) as first line, 40 (44.9%) received hypomethylating agents (HMA), and 15 (16.9%) received best supportive care (BSC). CR reached 37.1% (33) and was achieved in 67.6% of patients who received CMT as first line versus 25% for those who underwent HMA (P<0.001). The median OS for those who underwent CMT was 14.7 months (95% CI 2.7-26.7), HMA 11.7 months (95% CI 7.8-15.6), and BSC 0.7 months (95% CI 0-1.4; P<0.001). The stratified Charlson CCI evaluation did not show significant differences in relation to OS. Median OS for patients who underwent BMT was 36.5 months (95% CI 10.4-68.5) versus 4.1 months (95% CI 2.1-6.1) in non-BMT patients (P<0.001); this difference was statistically significant regardless of the first-line treatment established in the analysis by stratum. In the multivariate analysis, variables associated with OS were PS (HR 1.5 [95% CI 1-2.1]; P=0.03), CR (HR 0.5 [95% CI 0.3-0.9]; P=0.04) and BMT (HR 0.3 [95% CI 0.1-0.7]; P=0.003). A subgroup of patients with better OS is recognized: those with better PS at diagnosis who achieve CR with first-line treatment and have access to BMT. Incorporating new therapeutic strategies that are less toxic but with potential benefits to achieve higher CR rates could improve access to BMT.

Absolute lymphocyte count decreases with disease progression and is a potential prognostic marker for metastatic breast cancer.

Peripheral blood parameters such as the neutrophil-to-lymphocyte ratio (NLR) are prognostic markers for breast cancer patients. For instance, patients with a high NLR have a poor prognosis. Meanwhile, high absolute lymphocyte count (ALC) is reportedly a predictive factor for some chemotherapies. However, the underlying mechanisms behind how these markers relate to patient outcomes and how these markers change during the clinical course of patients with metastatic breast cancer (MBC) remains unknown. We retrospectively investigated 156 patients who were treated for MBC and eventually transitioned to best supportive care (BSC) at our hospital between January 2017 and December 2021. Changes in peripheral blood parameters during MBC treatments and their association with patient outcomes were examined. From the time of MBC diagnosis (baseline) through to the transition to BSC, ALC became significantly lower, while the NLR and platelet-to-lymphocyte ratio (PLR) became significantly higher (p < 0.001 for all). This association was independent of hormone receptor status. Cox proportional hazard modeling found patients with hormone receptor-negative and a lower baseline ALC had a significantly shorter overall survival (p = 0.030 and p = 0.019, respectively). We observed that peripheral blood markers gradually changed with MBC disease progression. Our data suggest that baseline ALC may be a potential prognostic marker after recurrence.

Estimation of time cost of anti-cancer drugs approved based on comparisons to best supportive care: A cross sectional analysis

BackgroundFinancial costs from cancer treatment are increasingly recognized, but what has historically been underrecognized is the time cost of therapy. We sought to estimate the time burden of anti-cancer drugs approved based on comparisons to best supportive care (BSC), with the assumption that without this drug, a patient could have been treated with observation, home palliative care or hospice services, with minimal time seeking medical care. MethodsWe searched all FDA approvals (2009 - March 2022) for randomized trials that used BSC as a treatment option for an anti-tumor drug in the metastatic setting and abstracted data on treatment related activities. We then estimated time spent on these activities using previously calculated times. ResultsOf the 13 drugs tested against BSC, nine studies demonstrated an improvement in median OS (median 2.1 months). The median monthly time spent for patients in the intervention arm of BSC trials was 15.8 h. ConclusionTime is a valuable resource for people who have cancer, but especially for patients who may have few to no remaining treatment options, and yet, we found that patients can spend up to 16 h in anti-cancer drug related activities per month. Policy summaryBecause survival outcomes are variable for patients being treated in later lines of therapy, time resources are a valuable consideration in the treatment plan.

Real-World Treatment Patterns and Clinical Outcomes in Canadian Patients with AML Unfit for First-Line Intensive Chemotherapy.

Acute myeloid leukemia (AML) is a hematological malignancy that predominantly affects the elderly. Prognosis declines with age. For those who cannot tolerate intensive chemotherapy, historically established treatment options have been hypomethylating agents (HMAs), low dose cytarabine (LDAC), and best supportive care (BSC). As the standard of care evolves for those unfit for intensive chemotherapy, there is a need to understand established treatment pathways, clinical outcomes and healthcare resource utilization in Canada. The CURRENT study was a retrospective chart review of AML patients not eligible for intensive chemotherapy who initiated first-line treatment between 1 January 2015 and 31 December 2018. Data were collected from 170 Canadian patients treated at six hematology centers, of whom 118 received systemic therapy and 52 received BSC as first-line treatment. Median overall survival was 8.58 months and varied from 2.96 months for BSC to 13.31 months for HMAs. Over 80% of patients had at least one outpatient visit, and 67% of patients receiving systemic therapy and 71% of those receiving BSC had at least one admission to hospital, during their first line of therapy. A total of 96 (81.4%) patients receiving first line systemic therapy and 39 (75.0%) of those receiving first line BSC had at least one red blood cell or platelet transfusion. These findings highlight the unmet need for novel therapies for patients ineligible for intensive chemotherapy.

Cost-effectiveness analysis of adjuvant therapy with atezolizumab in Chinese patients with stage IB-IIIA resectable NSCLC after adjuvant chemotherapy.

BackgroundAtezolizumab was first shown to significantly improve progression-free survival (PFS) after platinum-based chemotherapy in early-stage non-small cell lung cancer (NSCLC) in the IMpower010 Phase 3 trial. However, the cost-effectiveness and potential economic impact of atezolizumab treatment in Chinese patients are unknown.MethodsMarkov models were constructed based on follow-up data from the IMpower010 trial and assessed separately in the programmed cell death receptor ligand-1 (PD-L1) tumor cells (TC) ≥ 1% stage II – IIIA group, all stage II – IIIA groups, and the intention-to-treat (ITT) group (stage IB–IIIA). Efficacy and safety data were obtained from the IMpower010 trial, and costs and utility values were derived from the literature and local surveys to estimate their incremental cost-effectiveness ratios (ICERs) compared with willingness-to-pay (WTP) thresholds in scenarios implementing patient assistance programs (PAP) or drug price negotiations. Univariate sensitivity analysis and probabilistic sensitivity analysis (PSA) were performed to investigate the stability of the model results.ResultsCompared with best supportive care (BSC), atezolizumab produced an additional 0.45 quality-adjusted life-years (QALYs), 0.04 QALYs, and -0.0028 QALYs in the PD-L1 TC ≥ 1% stage II – IIIA group, all stage II – IIIA groups, and the ITT group, and the ICERs were 108,825.37/QALY, 1,028,538.22/QALY, and -14,381,171.55/QALY, respectively. The ICERs all exceeded the WTP threshold of $27,354 per QALY (three times the per capita gross domestic product of China in 2022), and univariate sensitivity analysis showed that the price of atezolizumab played a crucial role in the model results. PSA showed that the probability of cost-effectiveness of atezolizumab in the PD-L1 TC ≥ 1% stage II – IIIA group, all stage II – IIIA groups, and the ITT group increased with the increasing WTP threshold.ConclusionFrom the perspective of China’s health care system, in the PD-L1 TC ≥ 1% stage II – IIIA group, all stage II – IIIA groups, and the ITT group, the use of atezolizumab in the adjuvant treatment of patients with early-stage NSCLC after platinum-based chemotherapy is unlikely to be cost-effective. The implementation of PAP or price reduction negotiations for atezolizumab might be among the most effective measures to improve its cost-effectiveness.