Use of [177Lu]Lu-DOTA-TATE in the treatment of gastroenteropancreatic neuroendocrine tumours: Results of a UK cost-effectiveness modelling study.

AIM: To evaluate the cost-effectiveness of [177Lu]Lu-DOTA-TATE versus relevant comparators for the treatment of neuroendocrine tumours located in the gastrointestinal tract (GI-NETs) and the pancreas (P-NETs). MATERIALS AND METHODS: A three-state partitioned survival model was developed to perform a cost-utility analysis of [177Lu]Lu-DOTA-TATE versus standard of care (high dose Octreotide LAR), everolimus and sunitinib. Effectiveness data for SoC, everolimus and sunitinib were obtained from published Kaplan-Meier survival curves. Given a lack of head-to-head effectiveness data, matching adjusted indirect comparisons (MAICs) were performed to population-adjust [177Lu]Lu-DOTA-TATE survival data based on prognostic factors and derive estimates of relative effectiveness. Health state utilities were estimated from real-world evidence. Drug acquisition costs were taken from nationally published sources (BNF, NICE), and administration costs were based on treatment protocols in [177Lu]Lu-DOTA-TATE studies, combined with nationally published unit costs (PSSRU, DoH reference costs). Incidence of adverse events were estimated using published sources. A discount rate of 3.5% was applied to both utilities and costs, and deterministic and probabilistic sensitivity analyses were performed. Costs were included from an NHS perspective and presented in 2017/18 GBP (and PPP Euros for base case). RESULTS: In GI-NETs, the incremental cost-effectiveness ratio (ICER) of [177Lu]Lu-DOTA-TATE compared to SoC and everolimus was £26,528 (€27,672) and £24,145 (€25,186) per QALY, respectively. In P-NETs, the ICER of [177Lu]Lu-DOTA-TATE compared to SoC was £22,146 (€23,101) or £28,038 (€29,251) dependent on matched population, and £21,827 (€22,766) and £15,768 (€16,445) compared to everolimus and sunitinib, respectively. CONCLUSIONS: At a willingness to pay threshold of £30,000, [177Lu]Lu-DOTA-TATE is likely to be a cost-effective treatment option for GI-NET and P-NET patients versus relevant treatment comparators (NHS perspective).

Symptom Diaries of Patients with Midgut Neuroendocrine Tumors Treated with 177Lu-DOTATATE.

We report the impact of 177Lu DOTATATE treatment on abdominal pain, diarrhea, and flushing, symptoms that patients with advanced midgut neuroendocrine tumors (NETs) often find burdensome. Methods: All patients enrolled in the international randomized phase 3 Neuroendocrine Tumors Therapy (NETTER-1) trial (177Lu-DOTATATE plus standard-dose octreotide long-acting repeatable [LAR], n = 117; high-dose octreotide LAR, n = 114) were asked to record the occurrence of predefined symptoms in a daily diary. Change from baseline in symptom scores (mean number of days with a symptom) was analyzed using a mixed model for repeated measures. Results: Patients (intent-to-treat) who received 177Lu-DOTATATE experienced a significantly greater decline from baseline in symptom scores than patients who received high-dose octreotide LAR. For 177Lu-DOTATATE, the mean decline in days with abdominal pain, diarrhea, and flushing was 4.10, 4.55, and 4.52 days per 4 weeks, respectively, compared with 0.99, 1.44, and 2.54 days for high-dose octreotide LAR. The mean differences were 3.11 days (95% confidence interval, 1.35-4.88; P = 0.0007) for abdominal pain, 3.11 days (1.18-5.04; P = 0.0017) for diarrhea, and 1.98 days (0.08-3.88; P = 0.0413) for flushing, favoring 177Lu-DOTATATE. A positive repeated measures correlation was found between diary-recorded symptom scores and questionnaire-recorded pain, diarrhea, and flushing. Conclusion: In addition to efficacy and quality of life benefits, symptom diaries from NETTER-1 demonstrated that treatment with 177Lu DOTATATE was associated with statistically significant reductions in abdominal pain, diarrhea, and flushing, constituting the core symptoms of patients with progressive midgut NETs, compared with high-dose octreotide LAR, supporting a beneficial effect of 177Lu DOTATATE on HRQoL.

Cost-effectiveness of lutetium (177Lu) oxodotreotide vs everolimus in gastroenteropancreatic neuroendocrine tumors in Norway and Sweden.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a relatively rare and heterogenous group of tumors. Currently available treatment options for patients with progressive GEP-NETs include lutetium (177Lu) oxodotreotide (177Lu-Dotatate) and everolimus [as well as sunitinib for patients with pancreatic NETs (P-NETs)]. AIM: To perform a health economic analysis to determine the cost-effectiveness of 177Lu-Dotatate compared with everolimus in patients with unresectable or metastatic midgut-NETs or P-NETs in both Sweden and Norway. METHODS: Simulations were performed using a three-state partitioned survival model and analyses were performed separately for patients with midgut-NETs and P-NETs. Clinical input data were sourced from an indirect comparison that utilized survival data from clinical trials of 177Lu-Dotatate and everolimus. The analyses were performed from the healthcare payer perspective over a time horizon of 20 years. For Sweden, future costs and clinical outcomes were discounted at 3% per annum. For Norway, a discount rate of 4% per annum was applied. RESULTS: For Sweden, improved survival outcomes and higher lifetime costs with 177Lu-Dotatate resulted in an incremental cost-effectiveness ratio (ICER) of SEK 391194 per quality-adjusted life year (QALY) gained for midgut NETs and SEK 16764 per QALY gained for P-NETs for 177Lu-Dotatate compared with everolimus. For Norway, the corresponding ICERs were NOK 244444 per QALY gained and NOK 106451 per QALY gained, respectively. One-way sensitivity analyses revealed that the results were most sensitive to changes in drug acquisition costs and health state utility values. CONCLUSION: In both Sweden and Norway, from a healthcare provider perspective, 177Lu-Dotatate is likely to be considered cost-effective relative to everolimus for the treatment of patients with unresectable or metastatic, progressive midgut-NETs or P-NETs.

Quality of life in patients with gastroenteropancreatic tumours: A systematic literature review.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are slow-growing cancers that arise from diffuse endocrine cells in the gastrointestinal tract (GI-NETs) or the pancreas (P-NETs). They are relatively uncommon, accounting for 2% of all gastrointestinal malignancies. The usual treatment options in advanced GEP-NET patients with metastatic disease include chemotherapy, biological therapies, and peptide receptor radionuclide therapy. Understanding the impact of treatment on GEP-NET patients is paramount given the nature of the disease. Health-related quality of life (HRQoL) is increasingly important as a concept reflecting the patients' perspective in conjunction with the disease presentation, severity and treatment. AIM: To conduct a systematic literature review to identify literature reporting HRQoL data in patients with GEP-NETs between January 1985 and November 2019. METHODS: The PRISMA guiding principles were applied. MEDLINE, Embase and the Cochrane library were searched. Data extracted from the publications included type of study, patient population data (mid-gut/hind-gut/GI-NET/P-NET), sample size, intervention/comparators, HRQoL instruments, average and data spread of overall and sub-scores, and follow-up time for data collection. RESULTS: Forty-three publications met the inclusion criteria. The heterogeneous nature of the different study populations was evident; the percentage of female participants ranged between 30%-60%, whilst average age ranged from 53.8 to 67.0 years. Eight studies investigated GI-NET patients only, six studies focused exclusively on P-NET patients and the remaining studies involved both patient populations or did not report the location of the primary tumour. The most commonly used instrument was the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (n = 28) with consistent results across studies; the GI-NET-specific module Quality of Life Questionnaire-GINET21 was used in six of these studies. A number of randomised trials demonstrated no HRQoL changes between active treatment and placebo arms. The Phase III NETTER-1 study provides the best data available for advanced GEP-NET patients; it shows that peptide receptor radionuclide therapy can significantly improve GEP-NET patients' HRQoL. CONCLUSION: HRQoL instruments offer a means to monitor patients' general disease condition, disease progression and their physical and mental well-being. Instruments including the commonly used European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and GINET21 lack, however, validation and a defined minimal clinical important difference specifically for GI-NET and P-NET patients.

Adjunctive psychosocial therapies for the treatment of schizophrenia.

Antipsychotic pharmacotherapy is the standard of care for the treatment of schizophrenia. Although pharmacotherapy effectively improves some symptoms, others can remain. Pharmacotherapy alone also tends to produce only limited improvement in social functioning and quality of life. Supportive psychosocial therapies have been used as adjuncts to pharmacotherapy to help alleviate residual symptoms and to improve social functioning and quality of life. Additionally, therapies with psychoeducational components can focus on improving medication adherence and reducing relapse and rehospitalization. This review describes the major psychosocial therapeutic strategies that have been used effectively in patients with schizophrenia (cognitive-behavioral therapy, family intervention, social skills, and cognitive remediation), with emphasis on their utility in improving medication adherence. Therapies that integrate various psychosocial therapeutic approaches are also discussed. It is concluded that psychosocial therapy is an effective adjunct to pharmacotherapy for schizophrenia. However, these therapies vary significantly in the functional domains that they address. It is therefore important to identify the form of psychosocial intervention most likely to benefit the individual patient, and to recognize that the effectiveness of any psychosocial intervention could be influenced by such factors as the presence and severity of psychotic or affective symptoms or cognitive impairment.