Patient preference for deferasirox film-coated versus dispersible tablet formulation: a sequential-design phase 2 study in patients with thalassemia.

Iron chelation therapy (ICT) is the mainstay of treatment in patients with thalassemia requiring blood transfusions. This phase 2 JUPITER study evaluated patient preference between film-coated tablet (FCT) and dispersible tablet (DT) in transfusion-dependent thalassemia (TDT) or non-TDT (NTDT) patients treated with both formulations in a sequential manner. The primary endpoint was patient-reported preference for FCT over DT, while secondary outcomes included patient reported outcomes (PROs) evaluated by overall preference, and by age, thalassemia transfusion status, and previous ICT status. Out of 183 patients screened, 140 and 136 patients completed the treatment periods 1 and 2 of the core study, respectively. At week 48, the majority of patients preferred FCT over DT (90.3 vs. 7.5%; difference of percentage: 0.83 [95% confidence interval (CI), 0.75-0.89; P < 0.0001]). FCT scored better on secondary PROs and showed less severe gastrointestinal symptoms than DT, except in the change of modified Satisfaction with Iron Chelation Therapy (mSICT) preference scores, which were similar for both the formulations. Patients with TDT had stable ferritin levels, while it showed a downward trend up to week 48 in patients with NTDT on deferasirox treatment. Overall, 89.9% of patients reported ≥ 1 adverse event (AE), of which 20.3% experienced ≥ 1 serious AE. The most common treatment-emergent AEs were proteinuria, pyrexia, urine protein/creatinine ratio increase, diarrhea, upper respiratory tract infections, transaminase increase, and pharyngitis. Overall, this study reinforced the observations from the previous study by showing a distinct patient preference for FCT over DT formulation and further supported the potential benefits of life-long compliance with ICT.

TARGET: a survey of real-world management of chronic myeloid leukaemia across 33 countries.

Despite the availability of guidelines for the management of chronic myeloid leukaemia (CML), various issues may prevent their successful implementation. The TARGET survey examined real-world management of CML patients compared with international recommendations. This online survey was completed in 2017. Results were discussed by a Steering Committee (SC) of eight international haematologists, challenges were identified and practical solutions developed. Of the 1008 haematologists invited (33 countries), 614 completed the survey. Gaps regarding treatment efficacy and molecular monitoring were identified. Half of the physicians did not perform three-monthly testing of during the initial 12 months of treatment, citing cost as the major barrier, although they know it should be done. Treatment-free remission was not considered a primary treatment goal or as a priority factor influencing treatment decisions. European Leukemia Net guidelines interpretation was generally acceptable, but awareness regarding management of persistent adverse events was poor. Practical solutions proposed by the SC were mostly focused on enhancing physician education and awareness, or encouraging hospitals to work with the government, in order to improve the quality of BCR-ABL testing. Gaps in current CML management were identified compared with international recommendations, which the proposed practical solutions would help to address.

Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study.

Most patients with chronic myeloid leukemia (CML) treated with imatinib will relapse if treatment is withdrawn. We conducted a prospective clinical trial of imatinib withdrawal in 40 chronic-phase CML patients who had sustained undetectable minimal residual disease (UMRD) by conventional quantitative polymerase chain reaction (PCR) on imatinib for at least 2 years. Patients stopped imatinib and were monitored frequently for molecular relapse. At 24 months, the actuarial estimate of stable treatment-free remission was 47.1%. Most relapses occurred within 4 months of stopping imatinib, and no relapses beyond 27 months were seen. In the 21 patients treated with interferon before imatinib, a shorter duration of interferon treatment before imatinib was significantly associated with relapse risk, as was slower achievement of UMRD after switching to imatinib. Highly sensitive patient-specific BCR-ABL DNA PCR showed persistence of the original CML clone in all patients with stable UMRD, even several years after imatinib withdrawal. No patients with molecular relapse after discontinuation have progressed or developed BCR-ABL mutations (median follow-up, 42 months). All patients who relapsed remained sensitive to imatinib re-treatment. These results confirm the safety and efficacy of a trial of imatinib withdrawal in stable UMRD with frequent, sensitive molecular monitoring and early rescue of molecular relapse.

Chronic phase chronic myeloid leukemia patients with low OCT-1 activity randomized to high-dose imatinib achieve better responses and have lower failure rates than those randomized to standard-dose imatinib.

BACKGROUND: The functional activity of the organic cation transporter 1 (OCT-1) protein (OCT-1 activity) is an excellent predictor of molecular response and progression-free survival in patients with newly diagnosed chronic phase chronic myeloid leukemia treated with imatinib as front-line therapy. DESIGN AND METHODS: In this study the predictive value of OCT-1 activity in patients treated with imatinib 400 mg/day or 800 mg/day was evaluated in relation to trough imatinib plasma levels assessed in 100 patients enrolled in the Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) trial. RESULTS: The rate of major molecular responses by 24 months in patients on imatinib 400 mg/day was significantly higher in those with high OCT-1 activity than in those with low OCT-1 activity (low OCT-1 activity, 57% of patients; high OCT-1 activity, 100%; P < 0.001); the corresponding difference in patients treated with imatinib 800 mg/day did not reach statistical significance (low OCT-1 activity, 68%; high OCT-1 activity, 95%; P = 0.073). In addition, the combination of low trough imatinib levels (< 1200 ng/mL) and low OCT-1 activity defined a group of patients who had the lowest rates of major molecular response (47%) by 24 months compared to all other patients (81%, P = 0.009). These patients were also at the highest risk of failed imatinib therapy when compared to all other patients (P<0.001). CONCLUSIONS: High-dose imatinib leads to superior molecular responses in patients with low OCT-1 activity. In this group trough imatinib levels may define a group with inferior outcomes. Among patients with high OCT-1 activity, neither higher imatinib dose nor monitoring imatinib trough levels was found to be of significant clinical value. Hence OCT-1 activity determined prior to the start of therapy in newly diagnosed CML patients provides a valuable prognostic tool to determine the optimal up-front dose of imatinib in patients with newly diagnosed chronic phase chronic myeloid leukemia.

Enabling access to molecular monitoring for chronic myeloid leukemia patients is cost effective in China.

OBJECTIVE: To determine the cost effectiveness of molecular monitoring in patients with chronic myeloid leukemia in the chronic phase (CML-CP) compared to no molecular monitoring from a Chinese payer perspective. METHODS: Analyses were conducted using a semi-Markov model with a 50-year time horizon. Population data from multicenter registry-based studies of Chinese patients with CML-CP informed the model. Transition probabilities were based on time-to-event data from the literature. Utility values were obtained from published studies and were assumed to be the same for patients with and without molecular monitoring. Costs were based on values commonly used in the Chinese healthcare system, including drug acquisition, drug administration, follow-up, treatment for disease progression, molecular monitoring, and terminal care costs, and were in the local currency (2020 Chinese Yuan RMB [¥]). Outcomes were total life-years (LYs) and quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratio. RESULTS: Molecular monitoring was dominant to no molecular monitoring, with increased LYs (1.52) and QALYs (1.90) and costs savings (¥93,840) over a lifetime compared to no monitoring in discounted analyses. The opportunity of patients that receive molecular monitoring to discontinue treatment during treatment-free remission, an opportunity not afforded to those without molecular monitoring, was the principle driver of this result. Results were similar across multiple clinical scenarios. Particularly, molecular monitoring remained dominant even if the proportion of patients achieving deep molecular response (DMR) was reduced by 10%-30%, or the proportion of patients maintaining DMR for 1 year was reduced by 10%-30% or increased by 10%. Cost savings in these scenarios ranged from ¥62,230 to ¥103,964. CONCLUSIONS: Overall, this analysis demonstrates that adherence to guideline recommendations of regular molecular monitoring of patients with CML-CP treated with TKIs provides significant clinical benefit that leads to substantial cost savings compared to no molecular monitoring from the perspective of a Chinese payer. In a time where healthcare systems have limited resources to allocate to optimal patient care, investment in molecular monitoring is an ideal choice for improving patient benefits at a reduced cost.

A Phase Ib Study of Alpelisib or Buparlisib Combined with Tamoxifen Plus Goserelin in Premenopausal Women with HR-Positive HER2-Negative Advanced Breast Cancer.

PURPOSE: This study reports the MTD, recommended phase 2 dose (RP2D), and preliminary efficacy of alpelisib or buparlisib used in combination with tamoxifen plus goserelin in premenopausal patients with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC). PATIENTS AND METHODS: This study enrolled premenopausal women with HR+, HER2- ABC. Patients received tamoxifen (20 mg once daily) and goserelin acetate (3.6 mg every 28 days) with either alpelisib (350 mg once daily; n = 16) or buparlisib (100 mg once daily; n = 13) in 28-day cycles until MTD was observed. RESULTS: The criteria for MTD were not met for both alpelisib and buparlisib. The RP2D of alpelisib and buparlisib in combination with tamoxifen and goserelin were 350 mg and 100 mg, respectively. Both combinations met protocol-specified criteria for tolerability. The most common grade 3/4 treatment-emergent adverse events (TEAE) were hypokalemia (12.5%), hyperglycemia (6.3%), and rash (6.3%) for alpelisib and alanine aminotransferase increase (30.8%), aspartate aminotransferase increase (23.1%), and anxiety (15.4%) for buparlisib. TEAEs led to treatment discontinuation in 18.8% and 53.8% of alpelisib- and buparlisib-treated patients, respectively. Progression-free survival was 25.2 months in the alpelisib group and 20.6 months in the buparlisib group. CONCLUSIONS: The RP2Ds of alpelisib and buparlisib were 350 mg and 100 mg, respectively. No unexpected safety findings were reported. Although an early-phase study, data suggest that alpelisib plus endocrine therapy may be a potentially efficacious treatment that warrants further evaluation for premenopausal patients with HR+, HER2- ABC.See related commentary by Clark et al., p. 371.

Middle East observational study in metastatic soft tissue sarcoma: an epidemiological study on the treatment patterns (MOON).

PURPOSE: Soft tissue sarcomas (STS) are a heterogeneous group of rare mesenchymal neoplasms, accounting for < 1% of all newly diagnosed malignancies. These tumors can occur in almost any anatomic site though they most frequently occur in the extremities. The objective of the study was to describe the epidemiology, treatment paradigm, and real-world outcomes in the clinical management of metastatic STS (mSTS) in the Middle East and North Africa (MEA) region. METHODS: MOON was an observational, multicenter, retrospective patient chart review study which included 200 patients with mSTS in the final analysis. The primary objective of the study is exploratory, so it is presented using descriptive statistics. RESULTS: At the time of presentation, 62.0% patients had metastatic disease, 27.5% had received only their primary diagnosis and 10.0% had experienced a local recurrence. The most frequent STS localizations were lower extremities (74%), trunk (28.5%) and upper extremities (10.5%). Primary tumor was staged as T2b in the majority (60%) of patients. Surgical treatment was performed most often for the primary disease, whereas radiation therapy and chemotherapy were predominantly administered with palliative intent. A total of 38 patients received treatment with pazopanib. Thirteen adverse events (AEs) were attributed to pazopanib in eight patients. CONCLUSION: Adult patients treated for STS have al most equal gender ratio and mostly are middle aged. The majority of patients have metastatic disease and disease progression, and half of the patients died from the disease during the period of evaluation. This study obtained real-life data on the clinical management of STS in MEA countries which could be shared with the medical community.

Complementary and alternative medicine use in asthma: who is using what?

Consumer interest in complementary and alternative medicine (CAM) has grown dramatically in Western countries in the past decade. However, very few patients volunteer information about CAM use unless directly questioned by their health-care practitioner. Therefore, by being informed about the prevalence and modality of CAM use for asthma, as well as characteristics of users, health-care practitioners may be better able to identify patients who use CAM. In turn, this may facilitate proactive discussion and optimization of the patient's overall asthma management. This review aims to summarize the current knowledge about use of CAM by people with asthma, and to assess the applicability of the available studies to the broader asthmatic population. Computerized literature searches were conducted on Medline, Embase, Cochrane and Allied and Complementary Medicine (AMED) databases from their inception to 13 April 2005. Search terms included: complementary medicine/therapies, alternative medicine/therapies and asthma. The bibliographies of accessible articles were searched for further papers. Seventeen studies have examined the use of CAM by people with asthma. The reported level of use for adults ranged from 4% to 79%, and for children from 33% to 89%. Among the most commonly used CAMs were: breathing techniques, herbal products, homeopathy and acupuncture. There is no strong evidence for effectiveness for any of these modalities. There is little consistency among available prevalence studies making conclusions difficult. Nevertheless, the high rates of CAM use reported in some studies indicate that CAM use should be taken into account when managing patients with asthma.

Lack of awareness of need to clean CFC-free metered-dose inhalers.

BACKGROUND: Chlorofluorocarbon (CFC)-free metered-dose inhalers (MDIs) were introduced into Australia in 1999. Device care instructions were modified (e.g., CFC-free salbutamol inhalers to be washed weekly), but this information was not communicated directly to health care professionals. OBJECTIVE: This pilot study aimed to assess the level of awareness of device care protocols for CFC-free MDIs by patients and their pharmacists. SETTING AND DESIGN: Purchasers of CFC-free MDIs were recruited from four community pharmacies. They were interviewed regarding information sources, knowledge of propellant change, and awareness of and adherence to device care protocols. The dispensing pharmacists were interviewed for knowledge of CFC-free device care. The primary outcome variable was awareness of the relevant device care protocol. RESULTS: Thirty-nine patients were interviewed. Most patients (77%) were aware of the change to CFC-free propellant. Only nine patients (23%) were aware of the need to wash the device holder, and four patients (10% of total) complied with the specified protocol. One of the ten dispensing pharmacists could describe correct device care protocols for the CFC-free MDIs. CONCLUSIONS: Although most patients are aware that MDIs are now CFC-free, there is a low level of awareness of the device care required for these inhalers, and a very low rate of compliance with recommended practice. Although the clinical impact of failing to wash the device holder is unclear, this added instruction may have substantial implications for patient satisfaction and medication delivery. Pharmaceutical manufacturers need to highlight to health care professionals any clinically important changes in device care instructions, so that appropriate information may be passed on to patients.