Efficacy and safety of pasireotide LAR or everolimus alone, or in combination in patients with advanced carcinoids (NET) of the lung/thymus: Results from the randomized, phase 2 LUNA study

Ferollà, Piero; Brizzi, Mp; Meyer, Tim; Mansoor, Wasat; Cao, Cd; Berruti, Alfredo; Damiano,; Buikhuisen, Wieneke A.; Stankovic, Miona; Singh, Neha; Chiodini, E; Gislimberti, Gabriella; Öberg, Kjell; Baudin, Éric

doi:10.1093/annonc/mdw369.01

Cited by 6 publications

(9 citation statements)

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“…The data from our analysis supports the preliminary evidence of efficacy that was observed when everolimus was added to octreotide in patients with functional lung NET . The results from the three‐arm, randomized phase II LUNA trial (n = 112), comparing pasireotide in combination with everolimus vs everolimus alone and pasireotide alone in patients with typical and atypical lung or thymic carcinoids further support the efficacy of everolimus in this setting . The LUNA study achieved the preplanned statistical objective of a 9‐month PFS rate >20% in all three arms.…”

Section: Discussionmentioning

confidence: 99%

“…19 The results from the three-arm, randomized phase II LUNA trial (n = 112), comparing pasireotide in combination with everolimus vs everolimus alone and pasireotide alone in patients with typical and atypical lung or thymic carcinoids further support the efficacy of everolimus in this setting. 27 The LUNA study achieved the preplanned statistical objective of a 9-month PFS rate >20% in all three arms. The observed 9-month PFS rates were 39.0%, 33.3%, and 58.5% with a median PFS of 8.5, 12.5, and 11.8 months in pasireotide alone, everolimus alone, and combination arms, respectively.…”

Section: Probability Of Progression-free Survival (%)mentioning

confidence: 99%

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Everolimus in advanced, progressive, well‐differentiated, non‐functional neuroendocrine tumors: RADIANT‐4 lung subgroup analysis

et al. 2017

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In the phase III RADIANT‐4 study, everolimus improved median progression‐free survival (PFS) by 7.1 months in patients with advanced, progressive, well‐differentiated (grade 1 or grade 2), non‐functional lung or gastrointestinal neuroendocrine tumors (NETs) vs placebo (hazard ratio, 0.48; 95% confidence interval [CI], 0.35‐0.67; P < .00001). This exploratory analysis reports the outcomes of the subgroup of patients with lung NETs. In RADIANT‐4, patients were randomized (2:1) to everolimus 10 mg/d or placebo, both with best supportive care. This is a post hoc analysis of the lung subgroup with PFS, by central radiology review, as the primary endpoint; secondary endpoints included objective response rate and safety measures. Ninety of the 302 patients enrolled in the study had primary lung NET (everolimus, n = 63; placebo, n = 27). Median PFS (95% CI) by central review was 9.2 (6.8‐10.9) months in the everolimus arm vs 3.6 (1.9‐5.1) months in the placebo arm (hazard ratio, 0.50; 95% CI, 0.28‐0.88). More patients who received everolimus (58%) experienced tumor shrinkage compared with placebo (13%). Most frequently reported (≥5% incidence) grade 3‐4 drug‐related adverse events (everolimus vs. placebo) included stomatitis (11% vs. 0%), hyperglycemia (10% vs. 0%), and any infections (8% vs. 0%). In patients with advanced, progressive, well‐differentiated, non‐functional lung NET, treatment with everolimus was associated with a median PFS improvement of 5.6 months, with a safety profile similar to that of the overall RADIANT‐4 cohort. These results support the use of everolimus in patients with advanced, non‐functional lung NET. The trial is registered with ClinicalTrials.gov (no. NCT01524783).

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Section: Discussionmentioning

confidence: 99%

Section: Probability Of Progression-free Survival (%)mentioning

confidence: 99%

Everolimus in advanced, progressive, well‐differentiated, non‐functional neuroendocrine tumors: RADIANT‐4 lung subgroup analysis

et al. 2017

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“…There are now several case reports showing the efficacy of somatostatin analogues, including octreotide long-acting repeatable, alone or combined with other methods [64][65][66] . In the phase II LUNA trial, preliminary data were presented at ESMO in 2016: in patients with either lung or thymic carcinoids, the somatostatin multireceptor ligand pasireotide caused disease stabilisation in a significant proportion of patients, but it was unclear as to the effects in the specific subgroup of 8 thymic carcinoids [67] . According to recent guidelines, somatostatin analogues have been recommended as the optimal initial treatment option, especially with SRS-positive patients, when there is residual disease post-operatively.…”

Section: Anti-proliferative Therapymentioning

confidence: 99%

“…The mTOR inhibitor everolimus showed some efficacy in the subgroup of patients with lung carcinoids in the RADIANT-2 trial [70] , confirmed in the RADIANT-4 trial although only one thymic carcinoid was enrolled [71] . According to the preliminary data of the recent LUNA trial, everolimus produced disease stabilisation in many patients with lung and thymic tumours, although subgroup analysis is awaited [67] . With such few cases, the role of VEGFR tyrosine kinase inhibitors and mTOR inhibitors in treating thymic NENs has not been established, but certainly suggests they merit further consideration.…”

Section: Anti-proliferative Therapymentioning

confidence: 99%

Thymic Neuroendocrine Neoplasms: Biological Behaviour and Therapy

Jia

Šulentić

et al. 2017

Neuroendocrinology

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Thymic neuroendocrine neoplasms are rare tumours, but their management can often be highly problematic. While previously assumed to be essentially variants of bronchopulmonary (lung) carcinoids, they are generally more aggressive and more difficult to treat. Some 25% are associated with multiple endocrine neoplasia-1, while a higher proportion are associated with the ectopic ACTH syndrome, and occasionally both. We discuss the classification of these tumours, their biology as far as is known, and their clinical, biochemical and imaging features. We also review possible management options and suggest stratagems to optimise their treatment, which even today is far from optimal.

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“…No specific phase III trial for lung NETs was conducted so far, whereas the results of a randomised three-arm phase II trial enrolling just thoracic carcinoids have been presented at the last ESMO meeting (16). However, a large population of metastatic lung NETs was included in the RADIANT-4 study, comparing everolimus 10 mg/day plus best supportive care versus placebo plus best supportive care in patients with advanced progressing non-functioning NETs of gastrointestinal or lung origin (17).…”

Section: Everolimusmentioning

confidence: 99%

The role of multimodal treatment in patients with advanced lung neuroendocrine tumors

et al. 2017

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Lung neuroendocrine tumors (NETs) comprise typical (TC) and atypical carcinoids (AC). They represent the well differentiated (WD) or low/intermediate grade forms of lung neuroendocrine neoplasms (NENs). Unlike the lung poorly differentiated NENs, that are usually treated with chemotherapy, lung NETs can be managed with several different therapies, making a multidisciplinary interaction a key point. We critically discussed the multimodal clinical management of patients with advanced lung NETs. Provided that no therapeutic algorithm has been validate so far, each clinical case should be discussed within a NEN-dedicated multidisciplinary team. Among the systemic therapies available for metastatic lung NETs everolimus is the only approved drug, on the basis of the results of the phase III RADIANT-4 trial. Another phase III trial, the SPINET, is ongoing comparing lanreotide with placebo. Peptide receptor radionuclide therapy and chemotherapy were not studied within phase III trials for lung NETs, and they have been reported to be active within retrospective or phase II prospective studies. Temozolomide and oxaliplatin are two interesting chemotherapeutic agents in lung NETs. While some European Institutions were certificated as Centers of Excellence for gastroenteropancreatic NENs by the European Neuroendocrine Tumor Society (ENETS), an equivalent ENETS certification for lung NENs does not exist yet. Ideally a lung NEN-dedicated multidisciplinary tumor board should include NEN-dedicated medical oncologists, thoracic medical oncologist, thoracic surgeons, pathologists, interventional radiologists, endocrinologists, radiotherapists, interventional pneumologists, nuclear physician.

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Efficacy and safety of pasireotide LAR or everolimus alone, or in combination in patients with advanced carcinoids (NET) of the lung/thymus: Results from the randomized, phase 2 LUNA study

Cited by 6 publications

References 0 publications

Everolimus in advanced, progressive, well‐differentiated, non‐functional neuroendocrine tumors: RADIANT‐4 lung subgroup analysis

Everolimus in advanced, progressive, well‐differentiated, non‐functional neuroendocrine tumors: RADIANT‐4 lung subgroup analysis

Thymic Neuroendocrine Neoplasms: Biological Behaviour and Therapy

The role of multimodal treatment in patients with advanced lung neuroendocrine tumors

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