Patient-Reported Symptom Control of Diarrhea and Flushing in Patients with Neuroendocrine Tumors Treated with Lanreotide Depot/Autogel: Results from a Randomized, Placebo-Controlled, Double-Blind and 32-Week Open-Label Study

Fisher, George A.; Wolin, Edward M.; Liyanage, Nilani; Lowenthal, Susan Pitman; Mirakhur, Beloo; Pommier, Rodney F.; Shaheen, Montaser; Vinik, Aaron I.

doi:10.1634/theoncologist.2017-0284

Cited by 25 publications

(15 citation statements)

References 34 publications

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“…Previous post hoc analyses of the ELECT data have demonstrated that lanreotide patients were responsive with respect to their reported reduction in the symptoms of CS, and this was consistent across subgroups. In a post hoc analysis where patient-reported symptom data were combined to provide an average daily composite score, based on daily frequency and severity of symptoms, patients treated with lanreotide showed greater reductions in diarrhea or flushing compared with patients treated with placebo 19. Further subgroup analysis of ELECT found that the benefit of lanreotide compared to placebo, including greater CS symptom control, was consistent across treatment-naïve and octreotide-experienced patients, where lanreotide-treated subjects showed greater carcinoid symptom control in both samples 20.…”

Section: Discussionmentioning

confidence: 99%

<p>A Patient-Reported Outcomes Analysis Of Lanreotide In The Treatment Of NETs Patients With Carcinoid Syndrome: Evidence From The ELECT Trial</p>

Blot¹,

Duchateau

Lescrauwaet³

et al. 2019

PROM

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PurposeThe purpose of this analysis of patient-reported outcomes from the ELECT (Evaluation of Lanreotide Depot/Autogel Efficacy and Safety as a Carcinoid Syndrome Treatment) trial (NCT00774930) was to explore the effect of lanreotide on symptoms of carcinoid syndrome. Specifically, this post hoc analysis was designed to identify the most important patient-reported outcomes for patients in ELECT.MethodsThe post hoc analysis of ELECT, a placebo-controlled study of lanreotide in patients with neuroendocrine tumors, evaluated patient-reported outcomes during the double-blind phase of the trial, specifically daily diarrhea and flushing symptoms, octreotide rescue use, and the EORTC QLQ-C30 and QLQ-GINET21 questionnaires at baseline and week 12. Principal component (PC) analysis was applied on baseline data to identify independent variable clusters and clinically meaningful summary measures that highly correlated to these PCs. From those, the minimum clinical important differences were derived so to perform a responder analysis.ResultsThe three largest PCs captured 42.9% of the variation among baseline variables. The C30 summary score (C30-SS), diarrhea burden, and flushing burden were highly correlated with PC1, PC2, and PC3, respectively. Lanreotide patients were more likely to experience an improvement on the C30-SS (risk ratio [RR] 2.42; P=0.023), diarrhea burden (RR 2.85; P=0.005), and flushing burden (RR 1.39; P=0.31) compared to placebo patients. Lanreotide-treated patients have a higher probability of being a responder on at least one of the three domains of C30-SS, diarrhea burden, or flushing burden compared to placebo patients (RR 1.48; P=0.06).ConclusionThe higher response rates in the diarrhea burden are consistent with the previously reported effects of lanreotide on octreotide rescue medication use, while the findings of a greater efficacy of lanreotide vs placebo in the quality-of-life domains represent a novel aspect in the benefits of lanreotide.Trial registrationClinicalTrials.gov identifier: NCT00774930.

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Section: Discussionmentioning

confidence: 99%

<p>A Patient-Reported Outcomes Analysis Of Lanreotide In The Treatment Of NETs Patients With Carcinoid Syndrome: Evidence From The ELECT Trial</p>

Blot¹,

Duchateau

Lescrauwaet³

et al. 2019

PROM

Self Cite

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“…26 Clinical trials also support a reduction in the number of days patients on lanreotide experience diarrhea and/or flushing. 27 However, recent data from a large observational cohort shows that 43% of study subjects still experienced diarrhea after 6 months of lanreotide therapy compared to 44% at baseline. 28 The most common adverse effects associated with SSAs include nausea, abdominal cramps, loose stools, mild steatorrhea (due to meal-stimulated inhibition of pancreatic exocrine secretion and subclinical fat malabsorption), and flatulence.…”

Section: Historical Perspective Of Somatostatin Analogues and The Evolution Of The Lar-based Treatment Paradigmmentioning

confidence: 99%

Opportunities to Improve Symptom Control with Somatostatin Congeners in GEP-NETs: A Review of Key Issues

Anthony

O’Dorisio

2021

The Oncologist

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Octreotide acetate (octreotide) is the most prescribed and most studied somatostatin congener, or analog, for gastroenteropancreatic neuroendocrine tumors (GEP‐NETs) and carcinoid syndrome, the latter of which may be characterized by debilitating diarrhea and flushing. Approved in the U.S. more than 30 years ago, octreotide is widely used to control the symptoms of carcinoid syndrome and has been shown to demonstrate antiproliferative activity. The two formulations available in the U.S. include a subcutaneous immediate‐release (IR) injection introduced in 1989 and a long‐acting repeatable (LAR) intramuscular injection approved in 1999. Lanreotide depot (lanreotide), a more recent somatostatin congener, has been available in the U.S. since 2014. Despite widespread use of octreotide LAR, several key challenges exist with the current depot‐based treatment paradigm. Studies indicate that LAR formulations are associated with continued unmet patient needs, owing in part to a loss of bioactivity over time that may necessitate progressive supplemental treatment with IR octreotide to adequately control symptoms. Clinicians should understand the key differences in the pharmacokinetic profiles of the LAR and IR formulations that may contribute to bioactivity loss and somatostatin receptor desensitization. In addition, there is a need to re‐evaluate the role of IR octreotide in combination with depot therapy to provide consistent bioavailability and better control of carcinoid syndrome symptoms. The purpose of this review is to explore all these issues and to re‐establish a rationale for the IR formulation, particularly with respect to novel use cases and its use during the COVID‐19 pandemic. Implications for Practice There is a need to re‐evaluate the role of immediate‐release octreotide in combination with depot therapy to provide consistent bioavailability and better control of carcinoid syndrome symptoms.

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“…According to current guidelines, treatment with either octreotide or lanreotide is recommended as the initial first-line treatment in patients with CS (Table 5) [1]. If treatment with the standard dose is not effective, high-dose SSA therapy can be administered [57][58][59]. Tryptophan Hydroxylase Inhibitors: Telotristat, an oral inhibitor of tryptophan hydroxylase, has been investigated in TELESTAR and TELECAST phase III studies (Table 5) [72].…”

Section: Diarrhea Associated With Carcinoid Syndrome or Other Hormonamentioning

confidence: 99%

Section: Management Options and Treatment Strategiesmentioning

confidence: 99%

Differential Diagnosis and Management of Diarrhea in Patients with Neuroendocrine Tumors

Pusceddu

Rossi

Torchio

et al. 2020

JCM

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Diarrhea is a recurrent symptom in patients with neuroendocrine tumors (NETs) and can represent different etiologies; thus, differential diagnosis is challenging. This paper distinguishes the different causes of chronic diarrhea in patients with gastroenteropancreatic NETs, with the aim to identify the most appropriate therapeutic approach. Underlying causes of diarrhea can be multifactorial, including not only diarrhea that is related to specific hormonal hypersecretory syndromes, but also diarrhea that is secondary to the following: extensive surgery which can cause pancreatic exocrine insufficiency or short bowel syndrome, treatment with somatostatin analogs or other antineoplastic agents, and bile acid malabsorption. After initial management of diarrhea with general treatments (dietary modification, use of antidiarrheals), a proper differential diagnosis is necessary to treat patients with specific etiology-driven therapeutic approaches, such as somatostatin analogs, pancreatic enzyme replacement therapy, and tryptophan hydroxylase inhibitors. In conclusion, NETs should be considered in the differential diagnosis of patients suffering from chronic diarrhea, after the exclusion of more common etiologies. Furthermore, physicians should keep in mind that several different etiologies might be responsible for diarrhea occurrence in NET patients. A prompt diagnosis of the actual cause of diarrhea is necessary to guide the treatment and a multidisciplinary approach is mandatory.

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Patient-Reported Symptom Control of Diarrhea and Flushing in Patients with Neuroendocrine Tumors Treated with Lanreotide Depot/Autogel: Results from a Randomized, Placebo-Controlled, Double-Blind and 32-Week Open-Label Study

Cited by 25 publications

References 34 publications

<p>A Patient-Reported Outcomes Analysis Of Lanreotide In The Treatment Of NETs Patients With Carcinoid Syndrome: Evidence From The ELECT Trial</p>

<p>A Patient-Reported Outcomes Analysis Of Lanreotide In The Treatment Of NETs Patients With Carcinoid Syndrome: Evidence From The ELECT Trial</p>

Opportunities to Improve Symptom Control with Somatostatin Congeners in GEP-NETs: A Review of Key Issues

Differential Diagnosis and Management of Diarrhea in Patients with Neuroendocrine Tumors

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