Real-World Effectiveness, Safety, and Health-Related Quality of Life in Patients Receiving Adjuvant Nivolumab for Melanoma in Belgium and Luxembourg: Results of PRESERV MEL.

BACKGROUND: Nivolumab, an anti-programmed cell death 1 immuno-oncology therapy, is approved as an adjuvant treatment for patients with completely resected stage III or stage IV melanoma. PRESERV MEL (Prospective and REtrospective Study of nivolumab thERapy in adjuVant MELanoma) is a real-world observational study evaluating the effectiveness and safety of adjuvant nivolumab in patients with completely resected stage III or stage IV melanoma in clinical practice in Belgium and Luxembourg. METHODS: Patients were enrolled prospectively and retrospectively during a 2-year period (January 2019-January 2021), and will be followed for 5 years. The results reported here are for the second interim analysis (cutoff date 31 December 2021). The index date was the date of first administration of adjuvant nivolumab. Patients received nivolumab for up to 12 months per label. Outcomes included relapse-free survival (RFS), adverse events (AEs)/treatment-related AEs (TRAEs), and health-related quality of life (HRQoL; assessed in prospectively enrolled patients using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30), Functional Assessment of Cancer Therapy-Melanoma (FACT-M), and EQ-5D-3L instruments). HRQoL was evaluated at group level (mean change in scores from baseline based on minimally important differences) and individual patient level (percentage of patients with clinically important scores based on threshold of clinical importance). Outcomes were analyzed descriptively. RESULTS: The study enrolled 152 patients (125 prospective, 27 retrospective) at 15 hospitals in Belgium and Luxembourg. Minimum potential follow-up at time of analysis was 11.4 months. Median age was 60 years (range 29-85), and 53% of patients were male. At 12 and 18 months, the RFS rates were 74.7% (95% confidence interval (CI): 66.9-80.9) and 68.4% (95% CI: 60.0-75.5), respectively. Median RFS was not reached. Grade 3 or 4 TRAEs were reported in 14% of patients. AEs led to treatment discontinuation in 23% of patients. Deaths occurred in 3% of patients and were not related to treatment. Questionnaire completion rates for HRQoL were high at baseline (90-94%) and at 24 months (78-81%). In the group-level analysis for HRQoL, mean changes in scores from baseline remained stable and did not exceed prespecified thresholds for minimally important differences during and after treatment, except for a clinically meaningful improvement in FACT-M surgery subscale scores. In the individual patient-level analysis for EORTC QLQ-C30 subscales, the percentages of patients who reported clinically relevant scores for fatigue and cognitive impairment increased during treatment (at 9 months) compared with baseline. After treatment cessation (at 18 months), the percentage of patients who reported clinically relevant scores for fatigue decreased. However, the percentages of patients who reported clinically relevant scores for emotional, cognitive, and social impairment increased at 18 months compared with during treatment. Most patients with emotional impairment at 9 and 18 months did not experience disease recurrence (91% and 89%, respectively). CONCLUSIONS: These results confirm the real-world effectiveness and safety of nivolumab as an adjuvant treatment for patients with completely resected stage III or stage IV melanoma. Cancer-specific, disease-specific, and generic HRQoL were maintained during and after treatment. The percentage of patients reporting emotional and cognitive impairment increased after treatment cessation, emphasizing the need for further investigation and tailored supportive care in these patients.

Voriconazole treatment of invasive aspergillosis: real-world versus health-economic model results.

OBJECTIVE: The objective of this study was to assess, in a real-world setting, the predictive validity (in terms of clinical outcome and treatment cost) of the voriconazole arm of a health-economic model applied in the Belgian reimbursement submission for use of voriconazole in the treatment of invasive aspergillosis. METHODS: A non-interventional study was designed to prospectively collect clinical response and direct costs data related to the treatment of invasive aspergillosis with voriconazole (oral, intravenous) in real-world practice. The outcomes of this study were compared with the inputs and outputs of the health-economic model. For the analysis, unit costs of 2002 from the public payer's perspective, as used in the model, were applied. RESULTS: Data from 116 patients with invasive aspergillosis starting treatment with voriconazole were collected. At 12 weeks, there were similar rates of satisfactory clinical response for the observational study and the model, the latter based on the results of a clinical study (50% vs 53%, respectively). Overall mortality rates at 84 days were 42% in the observational study and 29% in the model. Average total healthcare cost associated with voriconazole treatment was lower in the observational study compared with the model for all patients. When the cost for all hospitalization days from the start until the end of the fungal infection was included in the analysis, the average total cost was euro19,674. When the cost for only those hospitalization days solely related to the fungal infection was included in the analysis, the average total cost was euro12,376. These costs are below the cost predicted by the model of euro21,298. CONCLUSIONS: This analysis demonstrates that the results provided in the voriconazole arm of the health-economic model were valid estimates with regard to real-world outcomes but with a slightly better survival rate and higher costs than in real life.

Cost-utility of pregabalin as add-on to usual care versus usual care alone in the management of peripheral neuropathic pain in Belgium.

BACKGROUND AND OBJECTIVES: The cost effectiveness of pregabalin as an add-on to the standard treatment of Belgian patients with post-herpetic neuralgia (PHN) had been demonstrated in a previously published Markov model. The purpose of this study was to update that model with more recent cost data and clinical evidence, and reevaluate the cost effectiveness from the payer's perspective of add-on pregabalin in a wider set of NeP conditions. METHODS: The model, featuring 4-week cycles and a 1-year time horizon, consisted in four possible health states: mild, moderate or severe pain and withdrawn from therapy. Three versions of the model were developed, using transition probabilities derived from pain scores reported in three placebo-controlled studies. The two treatment arms were 'usual care' or 'usual care + pregabalin'. Resource use and utility data were obtained from a chart review and unit costs from recent published data. The final outcome of the model was the incremental cost per quality-adjusted life-year (QALY) gained when adding pregabalin to standard care. RESULTS: Based on 1000 simulations, two versions of the model showed that pregabalin was dominant respectively in 94.8% and 67.2% of the simulations, while the incremental cost per QALY was below €32,000/QALY in respectively 99.1% and 94.6% of the simulations. The third version did not show cost effectiveness, despite an incremental cost of only €300 after 1 year. However, in the corresponding study, patients seemed less responsive to GABA analogs, since 55% of them had failed to respond to gabapentin before study inclusion. LIMITATIONS: The studies upon which the model is based have a short follow-up time as compared to the model horizon. The endpoints of two studies were only provided at the aggregated level and do not necessarily reflect the real practice. CONCLUSION: Based on this analysis, it can be concluded that from a Belgium payer perspective pregabalin offers a slight increase in quality of life in the studied populations as compared to standard care. Pregabalin is cost effective in the majority of cases except in one published clinical study, despite a low incremental cost per year (€300).