- Luspatercept Effective in Patients with Lower-Risk Myelodysplastic Syndromes
- Split-Fill Program for Oncology Oral Medications Is Cost-Saving
- Real-World Evidence Supports Patient Navigation in Cancer
Patients with anemia and lower-risk myelodysplastic syndromes (MDS) in whom first-line erythropoiesis-stimulating agents (ESAs) are not effective generally become transfusion dependent. Luspatercept-aamt (Reblozyl), a recombinant fusion protein that binds transforming growth factor beta superfamily ligands to reduce SMAD2 and SMAD3 signaling, was approved by the FDA in November 2019 and has been studied in this patient population with promising results.
In a new study, researchers evaluated the safety and efficacy of luspatercept in patients with lower-risk MDS with ring sideroblasts who had been receiving regular red blood cell (RBC) transfusions and whose disease was refractory to or was unlikely to respond to ESAs or who had discontinued therapy because of an adverse event (Fenaux P, et al. N Engl J Med. 2020;382:140-151).
The randomized, double-blind, placebo-controlled, phase 3 clinical trial MEDALIST included 229 patients with very low-risk, low-risk, or intermediate-risk MDS with ring sideroblasts who had been receiving regular RBC transfusions. Patients were randomized to luspatercept (N = 153), dosed at 1 mg/kg to 1.75 mg/kg, or to placebo (N = 76), administered subcutaneously every 3 weeks. The primary end point was transfusion independence for ≥8 weeks during weeks 1 through 24. The key secondary end point was transfusion independence for 12 weeks or longer, which was assessed during weeks 1 through 48 and weeks 1 through 24.
Transfusion independence for ≥8 weeks was achieved in 38% of patients in the luspatercept arm versus 13% in the placebo arm. In addition, 28% of patients in the luspatercept group achieved transfusion independence for ≥12 weeks versus 8% in the placebo group (during weeks 1-24, and 33% vs 12%, respectively, during weeks 1-48). By data cutoff, the median duration of the longest continuous response was 30.6 weeks with luspatercept versus 13.6 weeks with placebo.
The most common adverse events with luspatercept versus placebo were fatigue (27% vs 13%, respectively), diarrhea (22% vs 9%), asthenia (20% vs 12%), nausea (20% vs 8%), and dizziness (20% vs 5%). Overall, 65 patients who received luspatercept and 34 patients who received placebo had grade 3 or 4 adverse events.
“Patients with lower-risk myelodysplastic syndromes with ring sideroblasts for whom erythropoiesis-stimulating agents are not effective or are not an option have limited treatment options available beyond continued transfusions. Luspatercept significantly reduced the transfusion burden in a substantial proportion of these patients and was associated with mainly low-grade toxic effects,” concluded the researchers.
The discontinuation of oral oncology medications before the full-month supply has been finished results in medication waste, leading to increased costs for patients and for payers. Split fills allow for a 14- to 16-day supply for oral oncology medications rather than a full 28- to 30-day supply. Researchers compared the discontinuation rates, patient-reported adverse events, estimated pharmacy costs, and potential waste in patients with pharmacy benefit designs that included a split-fill option with patients who did not have this option (Staskon FC, et al. J Oncol Pract. 2019;15:e856-e862).
This retrospective cohort study included patients who were new to therapy with one of the 11 split-fill oncology oral medications within the managed program, between September 2015 and August 2017. Patients using split-fill and non–split-fill medications were matched by age, sex, state census areas, index medication, start date, and the use of >1 medication. The study included 2363 patients within the managed program who met the selection criteria for the 11 medications, and 671 patients from each group were matched.
The per-month medication discontinuation rates were assessed for each group. The monthly utilization trends indicated a significantly higher persistency rate for the split-fill cohort than the non–split-fill cohort in the second month (71.6% vs 67%, respectively; P <.001). Payers participating in a split-fill program had mean average wholesale price (AWP) savings of $2147.60 at 1 month and $928.60 at 6 months. Based on modeled waste, payers without a split-fill program could expect to save $2646.74 AWP monthly if they moved to the split-fill option.
Both cohorts had similar rates of adverse effects (55.3% for the split-fill cohort vs 56.4% for the non–split-fill cohort). The time until the first reported adverse effect trended toward being earlier for the split-fill group, but not significantly earlier.
“Even after noted modifications were made for new therapies, the split-fill patient managed component had lower discontinuation rates, significantly reduced pharmacy costs, and reduced potential wastage,” concluded the researchers. “By adopting a split-fill option, insurance payers have a means of reducing the pharmacy cost for new oncolytic therapy drugs, providing additional benefits to patients regarding copay, and addressing adverse events.”
Patient navigation is an increasingly recognized component of high-quality, patient-centered care. However, patient navigation in cancer programs is limited, often because of uncertainty about sustainable financial models to support these programs and defining the scope of practice. To demonstrate the benefits of patient navigation programs, researchers analyzed 5 real-world case studies (Kline RM, et al. J Oncol Pract. 2019;15:585-590).
Evidence showed that patient navigation increased patient retention in cancer programs. A pilot program at a northern California healthcare organization, for example, tested the differences in patient retention between patients with breast cancer for whom the patient navigation program was initiated earlier and later in the diagnostic continuum. The results showed that 35% fewer patients were lost to other health systems if they were in the patient navigation program from the point of a suspicious finding. A study of patients assisted by nurse navigators in the University of Pennsylvania Health System showed that these patients were 10% more likely to stay for treatment compared with those not in the program.
Patient navigation also increased patient and physician demands. The Sarah Cannon program, which is part of the Sarah Cannon Cancer Institute, had 59% growth in patients in the patient navigation program between 2017 and 2018, which correlates with increased patient volumes. In addition, loyalty among surgeons participating in the programs increased from 70% to >90% of surgeries performed when a surgeon used a nurse navigator.
Patient navigation was also associated with a reduction in unnecessary resource utilization, as demonstrated by the University of Alabama’s Patient Care Connect program. The percentage of emergency department visits, hospitalizations, and intensive care unit admissions declined by 6%, 7.9%, and 10.6% more per quarter, respectively, than the matched control patients. As a result, the costs for patients in the patient navigation program declined by $781.29 per quarter more than in the control group, resulting in an estimated 10:1 return on investment.
In addition, in a fee-for-service payment model, patient navigation was shown to generate financial benefits by significantly decreasing patients moving to other health facilities for their cancer care, based on data from the University of Pennsylvania, the Sarah Cannon Cancer Institute, and the northern California healthcare organization.
Key issues that remain for patient navigation programs include identifying what processes can best match navigator duties to specific patient needs and alternatives when navigators are unable to resolve patient concerns.
“Because evidence supports the importance of cancer PN [patient navigation] for patients and the financial benefit to practices and health systems, changes may be on the horizon that could transform PN from an intervention that a cancer practice has to offer to an intervention that a cancer practice wants to offer. This could certainly be described as a win-win-win for patients, practices, and providers,” concluded the researchers.