Selective Internal Radiation Therapy Using Y-90 Resin Microspheres for Metastatic Colorectal Cancer: An Updated Systematic Review and Network Meta-Analysis.

INTRODUCTION: This literature review and exploratory network meta-analysis (NMA) aimed to compare the clinical effectiveness and tolerability of selective internal radiation therapy (SIRT) using yttrium-90 (Y-90) resin microspheres, regorafenib (REG), trifluridine-tipiracil (TFD/TPI), and best supportive care (BSC) in adult patients with chemotherapy-refractory or chemotherapy-intolerant metastatic colorectal cancer (mCRC). METHODS: In light of recently published data, the literature was searched to complement and update a review published in 2018. Studies up to December 2022 comparing two or more of the treatments and reporting overall survival (OS), progression-free survival (PFS), or incidence of adverse events (AE) were included. The NMA compared hazard ratios (HRs) for OS and PFS using Markov chain Monte Carlo techniques. RESULTS: Fifteen studies were included, with eight studies added (none addressing SIRT). All active treatments improved OS in relation to BSC. SIRT had the longest OS among all treatments, although without statistically significant differences (HR [95% credible interval] for SIRT, 0.48 [0.27, 0.87]; TFD/TPI, 0.62 [0.46, 0.83]; REG, 0.78 [0.57, 1.05]) in a fixed effects model. Information regarding SIRT was insufficient for PFS analysis, and TFD/TPI was the best intervention (HR 2.26 [1.6, 3.18]). One SIRT study reported radioembolization-induced liver disease in > 10% of the sample; this was symptomatically managed. Non-haematological AEs (hand-foot skin reaction, fatigue, diarrhoea, hypertension, rash or desquamation) were more common with REG, while haematological events (neutropoenia, leukopenia, and anaemia) were more common with TFD/TPI. CONCLUSION: Current evidence supports SIRT treatment in patients with chemotherapy-refractory or chemotherapy-intolerant mCRC compared to newer oral agents, with comparable OS and low incidence of AEs.

Real-World Safety and Effectiveness of an 8-Week Regimen of Glecaprevir/Pibrentasvir in Patients with Hepatitis C and Cirrhosis.

INTRODUCTION: In 2019, an 8-week regimen of glecaprevir/ pibrentasvir (GLE/PIB) was FDA-approved for treatment of chronic hepatitis C (HCV) in patients with cirrhosis. We used data from the Chronic Hepatitis Cohort Study (CHeCS) to evaluate treatment response and adverse events among patients with HCV and cirrhosis under routine clinical care. METHODS: Using an intention-to-treat (ITT)/modified ITT (mITT) approach, endpoints were (1) sustained virological response (SVR) at 12 weeks (SVR12) post-treatment; and (2) adverse events (AEs)/serious AEs during treatment. Patients with cirrhosis from two CHeCS sites were included if they were prescribed GLE/PIB from August 2017 to June 2020. Detailed treatment and clinical data were collected. Patient baseline characteristics were described with mean/standard deviation (std) for continuous variables, and proportions for categorical variables. Analyses were propensity score adjusted. The final model retained variables that were significant with p value < 0.05. RESULTS: The ITT sample included 166 patients, with 43, 116, and 7 patients in the 8-week, 12-week, and > 12-week planned treatment groups. Among them, 159 had confirmed SVR (95.8%, LCL 93.2%). The mITT analysis included 160 patients after excluding 6 with unknown HCV RNA results; 159 achieved SVR (99.4%, LCL 98.3%). There were no significant differences in rates of SVR between the 8-week and 12-week regimens in either analysis, nor any association with patient characteristics. SAEs were experienced by 1 patient (2%) in the 8-week group, 7 (5%) in the 12-week group (including one death), and 2 (29%) in the > 12-week group; 4 patients (from the 12-week group) experienced serious AEs or hepatic events that were "likely attributable" to GLE/PIB treatment. CONCLUSION: An 8-week regimen of GLE/PIB is well tolerated and highly effective among US patients with HCV and cirrhosis receiving routine clinical care.

Usage of vildagliptin among patients with type 2 diabetes mellitus attending a public primary healthcare clinics in Kuala Selangor District, Selangor.

INTRODUCTION: Studies showed that vildagliptin can lower HbA1c levels by 0.8%-1%. However, there is limited data looking at vildagliptin use among suburban populations. The efficacy of vildagliptin use may differ among different populations, especially those with low socio-economic status. Thus, this study aimed to assess the HbA1c reduction after vildagliptin initiation, treatment patterns and the reason for its initiation among patients with type 2 diabetes mellitus attending outpatient clinics in Kuala Selangor District, Selangor. MATERIALS AND METHODS: This is a cross-sectional, retrospective study design. All patients who received vildagliptin in the Pharmacy Integrated Health System (PHIS) registry database from 2016 to 2021 were included as study samples. The exclusion criteria were being less than 18 years old and having type 1 diabetes mellitus. Patients' medical records were retrieved after sampling, and data were collected. One medical record was missing, thus SPSS analysis were performed on 144 vildagliptin users. RESULTS: In total, 84 females (58.3%) and 60 males (41.7%) with a mean age of 62.1 (±10.1) years were analysed in this study. Mean HbA1c pre-therapy was 8.5 ± 2.1%; while posttherapy 6 months demonstrated a mean HbA1c of 7.9 ± 1.8%. Use of vildagliptin alone or as an adjunct was associated with a mean reduction of 0.6% in HbA1c (p = 0.01). Factors influencing this HbA1c reduction were advancing age, specifically individuals aged 62 years and older (p = 0.02), patients who are already receiving insulin therapy (p=0.00) and those who express a willingness to commence insulin treatment during the counselling session prior to initiating the treatment plan (p = 0.00). Reasons for vildagliptin initiation documented by prescribers were non-insulin acceptance (n = 59, 40.97%), frequent hypoglycaemia (n = 6, 4.1%) and non-compliance with medications (n = 23, 15.9%). There was no association between demographic, medical background and reason for starting vildagliptin variables and HbA1c reduction (p < 0.001). CONCLUSION: This study showed that initiating vildagliptin alone or as an adjunct therapy significantly reduced HbA1c and is beneficial for uncontrolled diabetes patients. While advancing age, concurrent administration of insulin and the patients' willingness to accept insulin treatment prior to the commencement of therapy were the factors that influenced HbA1c reduction among patients receiving vildagliptin therapy, we recommend primary care providers prioritise all of the significant variables discovered before initiating vildagliptin for their patients.

Combined inhibition of MTAP and MAT2a mimics synthetic lethality in tumor models via PRMT5 inhibition.

Homozygous 5'-methylthioadenosine phosphorylase (MTAP) deletions occur in approximately 15% of human cancers. Co-deletion of MTAP and methionine adenosyltransferase 2 alpha (MAT2a) induces a synthetic lethal phenotype involving protein arginine methyltransferase 5 (PRMT5) inhibition. MAT2a inhibitors are now in clinical trials for genotypic MTAP-/- cancers, however the MTAP-/- genotype represents fewer than 2% of human colorectal cancers (CRCs), limiting the utility of MAT2a inhibitors in these and other MTAP+/+ cancers. Methylthio-DADMe-immucillin-A (MTDIA) is a picomolar transition state analog inhibitor of MTAP that renders cells enzymatically MTAP-deficient to induce the MTAP-/- phenotype. Here, we demonstrate that MTDIA and MAT2a inhibitor AG-270 combination therapy mimics synthetic lethality in MTAP+/+ CRC cell lines with similar effects in mouse xenografts and without adverse histology on normal tissues. Combination treatment is synergistic with a 104-fold increase in drug potency for inhibition of CRC cell growth in culture. Combined MTDIA and AG-270 decreases S-adenosyl-L-methionine and increases 5'-methylthioadenosine in cells. The increased intracellular methylthioadenosine:S-adenosyl-L-methionine ratio inhibits PRMT5 activity, leading to cellular arrest and apoptotic cell death by causing MDM4 alternative splicing and p53 activation. Combination MTDIA and AG-270 treatment differs from direct inhibition of PRMT5 by GSK3326595 by avoiding toxicity caused by cell death in the normal gut epithelium induced by the PRMT5 inhibitor. The combination of MTAP and MAT2a inhibitors expands this synthetic lethal approach to include MTAP+/+ cancers, especially the remaining 98% of CRCs without the MTAP-/- genotype.

Real-World Use of Fedratinib for Myelofibrosis Following Prior Ruxolitinib Failure: Patient Characteristics, Treatment Patterns, and Clinical Outcomes.

BACKGROUND: There is a lack of established clinical outcomes for patients with myelofibrosis (MF) receiving fedratinib following ruxolitinib failure. This study examined real-world patient characteristics, treatment patterns, and clinical outcomes of patients with MF treated with fedratinib following ruxolitinib failure in US clinical practice. PATIENTS AND METHODS: This retrospective patient chart review included adults with a physician-reported diagnosis of MF, who initiated fedratinib after discontinuing ruxolitinib. Descriptive analyses characterized patient characteristics, clinical outcomes, and treatment patterns from MF diagnosis through ruxolitinib and fedratinib treatment. RESULTS: Twenty-four physicians abstracted data for 150 eligible patients. Approximately 55.3% of the patients were male, 68.0% were White, and median age at MF diagnosis was 68 (range, 35-84) years. Median duration of ruxolitinib therapy was 7.6 (range, 0.7-65.5) months. At initiation of fedratinib, 88.0% of patients had palpable spleen and a mean spleen size of 16.0 (standard deviation [SD], 5.9) cm. Spleen size decreased by 19.4% to 13.2 (SD, 7.9) cm at month 3 (P = .0001) and by 53.4% to 7.2 (SD, 7.4) cm at month 6 (P = .01) of fedratinib treatment, respectively. Almost one-third (26.8%) of patients had achieved ≥ 50% spleen reduction by month 6. Mean number of symptoms also decreased significantly at month 3 (P < .0001) and month 6 (P = .01). CONCLUSION: Fedratinib appears to deliver spleen and symptom benefits in real-world patients with MF previously treated with ruxolitinib.

Lasofoxifene versus fulvestrant for ER+/HER2- metastatic breast cancer with an ESR1 mutation: results from the randomized, phase II ELAINE 1 trial.

BACKGROUND: Acquired estrogen receptor alpha (ER/ESR1) mutations commonly cause endocrine resistance in ER+ metastatic breast cancer (mBC). Lasofoxifene, a novel selective ER modulator, stabilizes an antagonist conformation of wild-type and ESR1-mutated ER-ligand binding domains, and has antitumor activity in ESR1-mutated xenografts. PATIENTS AND METHODS: In this open-label, randomized, phase II, multicenter, ELAINE 1 study (NCT03781063), we randomized women with ESR1-mutated, ER+/human epidermal growth factor receptor 2 negative (HER2-) mBC that had progressed on an aromatase inhibitor (AI) plus a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) to oral lasofoxifene 5 mg daily or IM fulvestrant 500 mg (days 1, 15, and 29, and then every 4 weeks) until disease progression/toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were safety/tolerability. RESULTS: A total of 103 patients received lasofoxifene (n = 52) or fulvestrant (n = 51). The most current efficacy analysis showed that lasofoxifene did not significantly prolong median PFS compared with fulvestrant: 24.2 weeks (∼5.6 months) versus 16.2 weeks (∼3.7 months; P = 0.138); hazard ratio 0.699 (95% confidence interval 0.434-1.125). However, PFS and other clinical endpoints numerically favored lasofoxifene: clinical benefit rate (36.5% versus 21.6%; P = 0.117), objective response rate [13.2% (including a complete response in one lasofoxifene-treated patient) versus 2.9%; P = 0.124], and 6-month (53.4% versus 37.9%) and 12-month (30.7% versus 14.1%) PFS rates. Most common treatment-emergent adverse events with lasofoxifene were nausea, fatigue, arthralgia, and hot flushes. One death occurred in the fulvestrant arm. Circulating tumor DNA ESR1 mutant allele fraction (MAF) decreased from baseline to week 8 in 82.9% of evaluable lasofoxifene-treated versus 61.5% of fulvestrant-treated patients. CONCLUSIONS: Lasofoxifene demonstrated encouraging antitumor activity versus fulvestrant and was well tolerated in patients with ESR1-mutated, endocrine-resistant mBC following progression on AI plus CDK4/6i. Consistent with target engagement, lasofoxifene reduced ESR1 MAF, and to a greater extent than fulvestrant. Lasofoxifene may be a promising targeted treatment for patients with ESR1-mutated mBC and warrants further investigation.

Usefulness Of Sofosbuvir And Daclatasvir Combination In The Treatment Of HCV Infection In Childhood Cancer Patients: Experience From A Tertiary Care Hospital.

Objectives: To determine the usefulness of Sofosbuvir-Daclatasvir combination in the treatment of hepatitis c virus infection in paediatric cancer.. METHODS: The retrospective study was conducted at the Oncology Department of the National Institute of Child Health, Karachi, and comprised medical charts of patients who received sofosbuvir and daclatasvir from January 2018 to January 2022. Efficacy was documented by clearance of hepatitis C virus ribonucleic acid as rapid viral response, early viral response and sustained viral response at weeks 4, 12 and 24, respectively. Drug efficacy was determined by monitoring and recording adverse effects. Chemotherapy protocol for the treatment of patients concomitantly receiving direct acting antivirals was modified while looking at drug-drug interactions. The total duration of direct acting antiviral therapy was 12 weeks. Data was analysed using SPSS 24. RESULTS: Of the 804 patients with different malignancies, 132(16.4%) were found positive for hepatitis C virus. Of them, 28(21.21%) patients were started on direct acting antivirals; 17(60.71%) boys and 11(39.28%) girls. The overall mean age was 9.93±6.12 years. The diagnosis was pre-B acute lymphoblastic leukaemia in 18(64.28%) cases, 16 (57.14%) were on maintenance chemotherapy, and 18(64.28%) had genotype 1. Pre- and post-treatment mean alanine transaminase levels were 328.00±324.00IU and 36.00±29.00IU, respectively (p=0.003). Pre- and post- treatment mean serum bilirubin levels were 3.13±3.95mg/dl and 0.61±0.21mg/dl (p=0.022). Rapid viral response was achieved in 26(92.85%) children, while early viral response and sustained viral response were achieved in all 28(100%) patients. Minor side effects were noted in 4(14.28%) patients and chemotherapy was continued in all 28(100%) cases as per the designed protocol. CONCLUSIONS: The sofosbuvir-daclatasvir combination was found to be effective in hepatitis C virus treatment in paediatric cancer patients.

Effectiveness and Safety of Eliglustat Treatment in Gaucher Disease: Real-life Unicentric Experience.

PURPOSE: The therapy and management of Gaucher disease (GD) have radically changed with the use of substrate reduction therapy, of which eliglustat is the most widely known drug, allowing it to overcome the limits of enzyme replacement therapy (ERT). The rarity of GD and the limited use of eliglustat outside clinical trials require further study of its strengths and weaknesses. METHODS: In this study, we evaluated the effectiveness and safety of eliglustat in a cohort of 12 patients with GD followed up in our center, reporting a reduction in both chitotriosidase (394.3 vs 181.1 nmol/h/mL, P = 0.027) and glucosylsphingosine values (45.1 vs 18.9 ng/mL, P <0.001) after at least 12 months of therapy compared with baseline, regardless of patient demographic characteristics and GD characteristics. FINDINGS: There were no drug-related serious adverse effects and no drug-related cardiac events. Most adverse events were mild and transient, mainly dyspepsia and abdominal pain. Of interest, we reported an absence of statistical difference in terms of response regarding glucosylsphingosine reduction in relation to naive or prior exposure to ERT (P = 0.296), which was confirmed also when patients were placed in naive and treated groups for <5 vs >5 years (P = 0.667). IMPLICATIONS: The use of eliglustat immediately after diagnosis may guarantee the best treatment for patients with milder phenotypes or with aggressive disease after an initial stabilization with ERT compared with ERT, which cannot adequately remove the disease burden despite the apparent response, thus potentially reducing future complications caused by substrate deposits.

Evaluation Of Left Ventricular Function After Sofosbuvir And Daclatasvir Regimen For Chronic Hepatitis C.

Objectives: To assess left ventricular functions by echocardiography after 12 weeks of sofosbuvir-daclatasvir combination therapy. Method: The prospective cohort study was conducted from December 2019 to December 2021 at Kafrelsheikh University Hospital, Egypt, and comprised adult patients of either gender who had been referred to the Cardiovascular Department for cardiac evaluation and were found to be eligible forsofosbuvir-daclatasvir combination therapy. The patients were classified into five groups according to cardiovascular risk factors. Group 1 had no risk factors; Group 2 had many risk factors; Group 3 had only hypertension; Group 4 had diabetes only; and Group 5 had smoking as the only risk. All patients were assessed at baseline and at the end of the 12-week of antiviral combination therapy sofosbuvir 400 mg once daily dose and daclatasvir 60 mg once daily dose. Parameters checked were left ventricular ejection fraction, global longitudinalstrain, wall motion abnormalities and diastolic function. Data was analysed using SPSS 23. RESULTS: Of the 200 patients, 104(52%) were females and 96(48%) were males. The age range was 34-81 years, and 18(9%) patients were aged >70 years. There were 78(39%) patientsin Group 1, 60(30%) in Group 2, 25(12.5%) in Group 3, Group 4 had 13(6.5%) and Group 5 had 24(12%) patients. There were no significant changes in mean ejection fraction, global longitudinal strain and wall motion abnormalities (p>0.05). Diastolic function had some significant parameters in each of the 5 groups (p<0.05). CONCLUSIONS: Sofosbuvir-daclatasvir combination therapy did not affect or impair left ventricular systolic or diastolic functions.

Cardiovascular Risk Assessment After Sofosbuvir And Daclatasvir Regimen For Chronic Hepatitis C Virus Infection.

Objectives: To assess cardiovascular risk after sofosbuvir and daclatasvir antiviral combination therapy in chronic hepatitis C virus patients. Method: The prospective cohortstudy was conducted at the Kafrelsheikh University Hospital, Egypt, from December 2019 to December 2021, and comprised adult patients of either gender with chronic hepatitis C virus and with minimum ejection fraction 40%. They were classified into groups according to their cardiovascular risk. Group 1 had individuals with no risk factors, Group 2 had patients with many risk factors, Group 3 had patients with only hypertension, Group 4 had those with diabetes alone, and Group 5 comprised smokers. All the patients were evaluated for the risk of major cardiovascular events at baseline and at the end of 12-week of antiviral combination therapy of sofosbuvir 400 mg once daily dose and daclatasvir 60 mg once daily dose. Data was analysed with SPSS version 23. RESULTS: Of the 200 patients, there were 96(48%) males and 104(52%) females. The age ranged 34-81 years. There were 78(39%) patients in Group 1; 20(25.6%) males and 58(74.4%) females with mean age 54.4±10.45 years. Group 2 had 60(30%) patients; 40(66.6%) males and 20(33.3%) females with mean age 59.57±9.1 years. Group 3 had 25(12.5%) patients; 3(12%) males and 22(88%) females with mean age 61.4±7.8 years. Group 4 had 13(6.5%) patients; 10(77%) males and 3(23%) females with mean age 55.4±10.4 years. Group 5 had 24(12%) patients who were all (100%) males with mean age 60.7±5.7 years. There were non-significant changes in the incidence of angina, arrhythmias or progression of dyspnoea (p>0.05). Echocardiography follow-up results showed non-significant changes in mean ejection fraction, global longitudinal strain and pulmonary artery pressure (p>0.05). CONCLUSIONS: Sofosbuvir and daclatasvir combination therapy wasfound to be safe in chronic hepatitis C virus patients regarding cardiac risks.

Prognostic factors in refractory metastatic colorectal cancer patients treated with Trifluridine/Tipiracil.

PURPOSE: The systemic treatment options for metastatic colorectal cancer (mCRC) are unsatisfactory, and the disease recurs despite the use of numerous medications and their combinations. Trifluridine/Tipiracil is a relatively new drug used in refractory mCRC. Little is known about its real-world effectiveness and prognostic and predictive factors. Therefore, this study aimed to develop a prognostic model for refractory mCRC treated with Trifluridine/Tipiracil. METHODS: We retrospectively evaluated the data from 163 patients who had received Trifluridine/Tipiracil as a third or fourth line of treatment for refractory mCRC. RESULTS: After starting Trifluridine/Tipiracil, 21.5% of patients survived one year, and the median overall survival after Trifluridine/Tipiracil initiation was 251 days (SD: 17.855; 95%CI: 216-286). Median progression-free survival after Trifluridine/Tipiracil initiation was 56 days (SD: 4.826; 95%CI 47-65). Moreover, the median overall survival from diagnosis was 1333 days (SD: 82.84; 95%CI: 1170-1495). In forward stepwise multivariate Cox regression analysis, initial radical treatment (HR = 0.552, 95% CI 0.372-0.819, p < 0.003), the number of cycles of first-line chemotherapy (HR = 0.978, 95% CI 0.961-0.995, p < 0.011), the number of cycles of second-line chemotherapy (HR = 0.955, 95% CI 0.931-0.98, p < 0.011), BRAF mutation (HR = 3.016, 95% CI = 1.207-7.537, p = 0.018), and hypertension (HR = 0.64, 95% CI = 0.44-0.931, p = 0.02) were all associated with survival after Trifluridine/Tipiracil initiation. Our model and model-based nomogram displayed an AUC of 0.623 for one-year survival estimation in the testing cohort. The C-index for the prediction nomogram was 0.632. CONCLUSION: We have developed a prognostic model for refractory mCRC treated with Trifluridine/Tipiracil based on five variables. Moreover, we reported a nomogram which could be used by oncologists in clinic visits on a daily basis.

Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer.

BACKGROUND: In a previous phase 3 trial, treatment with trifluridine-tipiracil (FTD-TPI) prolonged overall survival among patients with metastatic colorectal cancer. Preliminary data from single-group and randomized phase 2 trials suggest that treatment with FTD-TPI in addition to bevacizumab has the potential to extend survival. METHODS: We randomly assigned, in a 1:1 ratio, adult patients who had received no more than two previous chemotherapy regimens for the treatment of advanced colorectal cancer to receive FTD-TPI plus bevacizumab (combination group) or FTD-TPI alone (FTD-TPI group). The primary end point was overall survival. Secondary end points were progression-free survival and safety, including the time to worsening of the Eastern Cooperative Oncology Group (ECOG) performance-status score from 0 or 1 to 2 or more (on a scale from 0 to 5, with higher scores indicating greater disability). RESULTS: A total of 246 patients were assigned to each group. The median overall survival was 10.8 months in the combination group and 7.5 months in the FTD-TPI group (hazard ratio for death, 0.61; 95% confidence interval [CI], 0.49 to 0.77; P<0.001). The median progression-free survival was 5.6 months in the combination group and 2.4 months in the FTD-TPI group (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.54; P<0.001). The most common adverse events in both groups were neutropenia, nausea, and anemia. No treatment-related deaths were reported. The median time to worsening of the ECOG performance-status score from 0 or 1 to 2 or more was 9.3 months in the combination group and 6.3 months in the FTD-TPI group (hazard ratio, 0.54; 95% CI, 0.43 to 0.67). CONCLUSIONS: Among patients with refractory metastatic colorectal cancer, treatment with FTD-TPI plus bevacizumab resulted in longer overall survival than FTD-TPI alone. (Funded by Servier and Taiho Oncology; SUNLIGHT ClinicalTrials.gov number, NCT04737187; EudraCT number, 2020-001976-14.).

Newly diagnosed hepatitis C infection after pancreas transplantation with multiple treatment failures.

This case represents the first report of a detected hepatitis C virus (HCV) infection following a pancreas transplantation that failed two different sofosbuvir (SOF)-based treatments. We present the case of a woman in her 30s with a history of kidney transplantation, who developed viremic symptoms 3 months after pancreas transplantation and with two subsequent negative HCV antibody tests. Further work-up revealed a positive HCV RNA test (genotype 1A, treatment naive). Two different direct-acting antiviral agents regimes with SOF failed in our case, and the patient achieved a sustained virological response with a 16-week course of glecaprevir/pibrentasvir.

A UK cost-effectiveness analysis of trifluridine/tipiracil for heavily pretreated metastatic gastroesophageal cancers.

Background: The current work was designed to estimate the cost-effectiveness of trifluridine/tipiracil (T/T) versus best supportive care (BSC) for patients with advanced stage or metastatic gastroesophageal cancer (mGC) from a UK perspective. Materials & methods: A partitioned survival analysis was undertaken using data from the phase III TAGS trial. A jointly fitted lognormal model was selected for overall survival and individual generalized gamma models were chosen for progression-free survival and time-to-treatment-discontinuation. The primary outcome was the cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were undertaken to investigate uncertainty. Results: Compared with BSC, T/T was associated with a cost per QALY gained of £37,907. Conclusion: T/T provides a cost-effective treatment option for mGC in the UK setting.

An evaluation of fedratinib for adult patients with newly diagnosed and previously treated myelofibrosis.

INTRODUCTION: Myelofibrosis (MF) is a life-shortening myeloproliferative neoplasm that has multiple features such as clonal proliferation, fibrosis and splenomegaly. Until recently, ruxolitinib, a Janus Kinase (JAK) 1/2 inhibitor was the only targeted therapy approved for transplant-ineligible patients with MF and who require treatment for symptoms and/or splenomegaly. However, the discontinuation rate with ruxolitinib at 3 to 5 years is high and mostly due to loss of response or toxicity, and these patients had no subsequent treatment. AREAS COVERED: Fedratinib, a selective JAK2 inhibitor, was approved by the Food and Drug Administration (FDA) in August 2019 for the treatment of intermediate-2 or high-risk primary or secondary MF, regardless of prior JAK inhibitor treatment for the management of symptoms and splenomegaly. We discuss herein the development of fedratinib and its pharmacology and pharmacokinetics as well as the clinical development and the future directions. We used PubMed for the search of articles related to fedratinib and myelofibrosis. EXPERT OPINION: Fedratinib provided a second-line treatment for patients with MF who failed or discontinued ruxolitinib. New combinations of JAK inhibitors with other targeted therapies are a must in order to improve the management of MF.

Gaucher Disease Types I and III Responded Well to Substrate Reduction Therapy Using Eliglustat.

Gaucher disease (GD) causes the accumulation of glucocerebrosides in various organs, resulting in hepatosplenomegaly, anemia, decreased platelet counts, and bone disorders. Glucosylsphingosine accumulates in the brain and causes central nervous system (CNS) disorders. GD can be classified into types I (without CNS disorders), II, and III. Substrate reduction therapy (SRT) is an oral therapy that improves patients' quality of life; however, its effect on type III GD is unknown. We administered SRT to GD types I and III patients and found it effective. Malignancy is a late complication of GD, but this is the first report of Barrett adenocarcinoma.