Safety and QOL in Patients with Advanced NET in a Phase 3b Expanded Access Study of Everolimus

Pavel, Marianne; Unger, Nicole; Borbath, Ivan; Ricci, Sergio; Hwang, Tsann‐Long; Brechenmacher, Thomas; Park, Jinhee; Herbst, Fabian; Beaumont, Jennifer L.; Bechter, Oliver

doi:10.1007/s11523-016-0440-y

Cited by 26 publications

(26 citation statements)

References 15 publications

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“…The age of patients in this study is similar to that reported in the pivotal RADIANT-3 phase III clinical trial of everolimus [9] and a recent phase IIIb study that evaluated safety and HRQoL in patients with advanced NETs treated with everolimus in an expanded access protocol [17]. About 30% of patients in our study had a performance status of 0 at baseline, which is lower than the phase III trial (67%) [9] and expanded access study (56%) [17]. This difference may reflect the real-world nature of the OBLIQUE population, with patients limited in their everyday activities to a greater extent than patients included in clinical trials.…”

Section: Discussionmentioning

confidence: 64%

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Observational Study to Assess Quality of Life in Patients with Pancreatic Neuroendocrine Tumors Receiving Treatment with Everolimus: The OBLIQUE Study (UK Phase IV Trial)

et al. 2019

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Background/Aims: To assess health-related quality of life (HRQoL), treatment patterns, and clinical outcomes of adult (≥18 years) patients with advanced (unresectable or metastatic) pancreatic neuroendocrine neoplasms (PanNENs) treated with everolimus in routine clinical practice. Methods: In a prospective, non-interventional, multi-center study patients administered at least one 10 mg dose of everolimus were evaluated for change in HRQoL (EORTC QLQ-C30 Global Health Status scale) from baseline after 6 months treatment (primary endpoint). Secondary endpoints included disease-specific HRQoL measures (EORTC QLQ-G.I.NET21), clinical outcomes, everolimus treatment patterns, and safety. Results: Forty-eight patients were recruited (between August 2013 and March 2015); the median treatment duration was 27.8 months. EORTC QLQ-C30 Global Health score was not significantly different from baseline after 6 months of treatment (mean difference –1.9 points, p = 0.660, n = 30). In pairwise analyses, the only significant changes in HRQoL from baseline were for EORTC QLQ-C30 physical functioning score at month 3 (adjusted mean difference –8.8 points, p = 0.002, n = 36) and the EORTC QLQ-G.I.NET21 disease-related worries scores at months 1 and 2 (adjusted mean differences: –11.5 points [p = 0.001, n = 44] and –8.8 points [p = 0.017, n = 43], respectively). Disease progression or death was recorded in 44.4% (n = 20/45) patients during follow-up; median progression-free survival was 25.1 months and the cumulative survival rate at 3 years was 71%. No new safety signals were detected. Conclusions: The OBLIQUE study demonstrates that HRQoL is maintained in patients with PanNENs during treatment with everolimus in a UK real-world setting. This study adds to the limited HRQoL data available in this patient group.

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Section: Discussionmentioning

confidence: 64%

“…everolimus [17]. A further patient reported outcome study in 44 outpatients (single-center in Italy) with PanNENs receiving either no treatment, or somatostatin analogs (with or without radiometabolic therapy) showed that over a 4-month period, patients had a good physical, but impaired mental component of HRQoL [11].…”

Section: Discussionmentioning

confidence: 99%

Observational Study to Assess Quality of Life in Patients with Pancreatic Neuroendocrine Tumors Receiving Treatment with Everolimus: The OBLIQUE Study (UK Phase IV Trial)

et al. 2019

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“…Pulmonary toxicity (n=5) and infection/sepsis (n=3) were the most common fatal AEs that caused everolimus-related death[22,23,75,76,93]. Though patient-reported tolerance with everolimus treatment was reported to be poorer than SSA[165], health-related QOL was well maintained in large clinical trials[71,79,166]. These results strongly support the general tolerability of everolimus by most patients in both the clinical trial setting and real-world setting.…”

Section: Safety Of Everolimus (Table 6)mentioning

confidence: 99%

Everolimus in the treatment of neuroendocrine tumors: efficacy, side-effects, resistance, and factors affecting its place in the treatment sequence

Lee

Ito

Jensen

2018

Expert Opinion on Pharmacotherapy

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Introduction: Since the initial approval of everolimus in 2011, there have been a number of important changes in therapeutic/diagnostic modalities as well as classification/staging systems of neuroendocrine tumors (NETs), which can significantly impact the use of everolimus in patients with advanced NETs. Areas covered: The efficacy of everolimus monotherapy and combination therapy demonstrated in clinical studies involving patients with advanced NETs are reviewed. Several factors affecting everolimus’ use are described including: the development and routine use of NET classification/staging systems; widespread use of molecular imaging modalities; side-effects; drug resistance; and the availability of other treatment options. Furthermore, the current position of everolimus in the treatment approach is discussed, taking into account the recommendations from the recent guidelines. Expert opinion: Although everolimus demonstrated its high efficacy and tolerability in the RADIANT trials and other clinical studies, there still remain a number of controversies related to everolimus treatment in the management of NETs. The synergistic anti-growth effect of other agents in combination with everolimus or its effect on overall survival have not been established. The appropriate order of the use of everolimus in the treatment of advanced NETs still remains unclear, which needs to be defined in further studies and will be addressed in the new guidelines.

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“…Ramage et al[ 54 ] used the EQ-5D-5L (in addition to EORTC QLQ-C30 and GINET21), with no significant difference for the composite health index or self-rated (global) health score noted between baseline and 6-mo treatment with everolimus. The EQ-5D VAS was employed in two studies: Kulke et al[ 55 ] examined patients receiving repeated 6-weekly cycles of oral sunitinib, noting no significant difference in VAS scores over the study period, whilst Pavel et al[ 56 ] reported a reduced mean VAS from baseline to end of treatment with oral everolimus (10 mg daily, in 28-d cycles) in non-P-NET patients (63.9 ± 19.0 vs 55.3 ± 23.0, respectively) compared to P-NET patients (68.8 ± 19.9 vs 66.5 ± 20.6, respectively). The FACIT-D measure is a symptom-specific measure used by Kvols et al[ 29 ] in a Phase II, open-label, multicentre prospective study of self-administered pasireotide.…”

Section: Resultsmentioning

confidence: 99%

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

Watson¹,

Tallentire²,

Srirajaskanthan

et al. 2020

WJG

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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.

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Safety and QOL in Patients with Advanced NET in a Phase 3b Expanded Access Study of Everolimus

Abstract: EudraCT no. 2010-023032-17.

Cited by 26 publications

References 15 publications

Observational Study to Assess Quality of Life in Patients with Pancreatic Neuroendocrine Tumors Receiving Treatment with Everolimus: The OBLIQUE Study (UK Phase IV Trial)

Observational Study to Assess Quality of Life in Patients with Pancreatic Neuroendocrine Tumors Receiving Treatment with Everolimus: The OBLIQUE Study (UK Phase IV Trial)

Everolimus in the treatment of neuroendocrine tumors: efficacy, side-effects, resistance, and factors affecting its place in the treatment sequence

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

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