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

N. Fazio, R. Buzzoni, G. Delle Fave, M.E. Tesselaar, E. Wolin, E. Van Cutsem, P. Tomassetti, J. Strosberg, M. Voi, L. Bubuteishvili-Pacaud, A. Ridolfi, F. Herbst, J. Tomasek, S. Singh, M. Pavel, M.H. Kulke, J.W. Valle, J.C. Yao

Research output: Contribution to journalArticle

Abstract

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
Original languageEnglish
Pages (from-to)174-181
Number of pages8
JournalCancer Science
Volume109
Issue number1
DOIs
Publication statusPublished - 2018

Fingerprint

Neuroendocrine Tumors
Disease-Free Survival
Placebos
Confidence Intervals
Lung
Everolimus

Keywords

  • everolimus
  • lung carcinoid
  • neuroendocrine tumors
  • progression-free survival
  • RADIANT-4
  • antineoplastic agent
  • adult
  • advanced cancer
  • aged
  • anemia
  • aphthous stomatitis
  • Article
  • asthenia
  • body weight loss
  • cancer chemotherapy
  • cancer regression
  • cancer survival
  • clinical outcome
  • cohort analysis
  • controlled study
  • coughing
  • decreased appetite
  • diarrhea
  • drug efficacy
  • drug safety
  • dysgeusia
  • dyspnea
  • exploratory research
  • fatigue
  • female
  • fever
  • glossitis
  • human
  • hyperglycemia
  • infection
  • lung cancer
  • major clinical study
  • male
  • median survival time
  • mouth ulcer
  • multicenter study (topic)
  • nausea
  • neuroendocrine tumor
  • peripheral edema
  • phase 3 clinical trial (topic)
  • pneumonia
  • post hoc analysis
  • priority journal
  • progression free survival
  • pruritus
  • randomized controlled trial (topic)
  • rash
  • side effect
  • stomatitis
  • treatment response
  • xerostomia
  • clinical trial
  • disease free survival
  • double blind procedure
  • lung tumor
  • middle aged
  • multicenter study
  • phase 3 clinical trial
  • prospective study
  • randomized controlled trial
  • treatment outcome
  • very elderly
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents
  • Disease-Free Survival
  • Double-Blind Method
  • Everolimus
  • Female
  • Humans
  • Lung Neoplasms
  • Male
  • Middle Aged
  • Neuroendocrine Tumors
  • Prospective Studies
  • Treatment Outcome

Cite this

Everolimus in advanced, progressive, well-differentiated, non-functional neuroendocrine tumors: RADIANT-4 lung subgroup analysis. / Fazio, N.; Buzzoni, R.; Delle Fave, G.; Tesselaar, M.E.; Wolin, E.; Van Cutsem, E.; Tomassetti, P.; Strosberg, J.; Voi, M.; Bubuteishvili-Pacaud, L.; Ridolfi, A.; Herbst, F.; Tomasek, J.; Singh, S.; Pavel, M.; Kulke, M.H.; Valle, J.W.; Yao, J.C.

In: Cancer Science, Vol. 109, No. 1, 2018, p. 174-181.

Research output: Contribution to journalArticle

Fazio, N, Buzzoni, R, Delle Fave, G, Tesselaar, ME, Wolin, E, Van Cutsem, E, Tomassetti, P, Strosberg, J, Voi, M, Bubuteishvili-Pacaud, L, Ridolfi, A, Herbst, F, Tomasek, J, Singh, S, Pavel, M, Kulke, MH, Valle, JW & Yao, JC 2018, 'Everolimus in advanced, progressive, well-differentiated, non-functional neuroendocrine tumors: RADIANT-4 lung subgroup analysis', Cancer Science, vol. 109, no. 1, pp. 174-181. https://doi.org/10.1111/cas.13427
Fazio, N. ; Buzzoni, R. ; Delle Fave, G. ; Tesselaar, M.E. ; Wolin, E. ; Van Cutsem, E. ; Tomassetti, P. ; Strosberg, J. ; Voi, M. ; Bubuteishvili-Pacaud, L. ; Ridolfi, A. ; Herbst, F. ; Tomasek, J. ; Singh, S. ; Pavel, M. ; Kulke, M.H. ; Valle, J.W. ; Yao, J.C. / Everolimus in advanced, progressive, well-differentiated, non-functional neuroendocrine tumors: RADIANT-4 lung subgroup analysis. In: Cancer Science. 2018 ; Vol. 109, No. 1. pp. 174-181.
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title = "Everolimus in advanced, progressive, well-differentiated, non-functional neuroendocrine tumors: RADIANT-4 lung subgroup analysis",
abstract = "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",
keywords = "everolimus, lung carcinoid, neuroendocrine tumors, progression-free survival, RADIANT-4, antineoplastic agent, adult, advanced cancer, aged, anemia, aphthous stomatitis, Article, asthenia, body weight loss, cancer chemotherapy, cancer regression, cancer survival, clinical outcome, cohort analysis, controlled study, coughing, decreased appetite, diarrhea, drug efficacy, drug safety, dysgeusia, dyspnea, exploratory research, fatigue, female, fever, glossitis, human, hyperglycemia, infection, lung cancer, major clinical study, male, median survival time, mouth ulcer, multicenter study (topic), nausea, neuroendocrine tumor, peripheral edema, phase 3 clinical trial (topic), pneumonia, post hoc analysis, priority journal, progression free survival, pruritus, randomized controlled trial (topic), rash, side effect, stomatitis, treatment response, xerostomia, clinical trial, disease free survival, double blind procedure, lung tumor, middle aged, multicenter study, phase 3 clinical trial, prospective study, randomized controlled trial, treatment outcome, very elderly, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Disease-Free Survival, Double-Blind Method, Everolimus, Female, Humans, Lung Neoplasms, Male, Middle Aged, Neuroendocrine Tumors, Prospective Studies, Treatment Outcome",
author = "N. Fazio and R. Buzzoni and {Delle Fave}, G. and M.E. Tesselaar and E. Wolin and {Van Cutsem}, E. and P. Tomassetti and J. Strosberg and M. Voi and L. Bubuteishvili-Pacaud and A. Ridolfi and F. Herbst and J. Tomasek and S. Singh and M. Pavel and M.H. Kulke and J.W. Valle and J.C. Yao",
note = "Cited By :2 Export Date: 5 February 2019 CODEN: CSACC Correspondence Address: Fazio, N.; European Institute of Oncology, IRCCSItaly; email: nicola.fazio@ieo.it Chemicals/CAS: everolimus, 159351-69-6; Antineoplastic Agents; Everolimus Funding details: European Society for Medical Oncology, ESMO Funding details: Bayer Funding details: Novartis Funding details: Ipsen Fund Funding details: Boehringer Ingelheim Funding details: Sanofi Funding details: Pfizer Funding details: Novartis Pharmaceuticals Corporation, NPC Funding text 1: This research was presented in part at the Annual European Neuroendocrine Tumors Society (ENETS) Conference, March 9-11, 2016 in Barcelona, Spain and the European Society of Medical Oncology (ESMO) Congress, October 7-11, 2016, Copenhagen, Denmark. Funding text 2: Nicola Fazio received honoraria from Novartis, Ipsen, and Pfizer, and his institution received research funding from Novartis and Merck Serono. Gianfranco Delle Fave received honoraria and research funding from Novartis. Margot Tesselaar received research funding from Novartis. Eric Van Cutsem received research funding from Novartis, Ipsen, Sanofi, Roche, Bayer, and Boehringer. Jonathan Strosberg received research funding from Novartis and Ipsen and his institution received research funding from Novartis. Maurizio Voi and Fabian Herbst are employees of Novartis and have stock ownership from Novartis. Lida Bubuteishvili-Pacaud and Antonia Ridolfi are employees of Novartis. Simron Singh received research funding from Novartis. Marianne Pavel received honoraria from Novartis and her institution received research funding from Novartis. Juan W. Valle received honoraria and travel reimbursement from Novartis, and his institution received research funding from Novartis. James C. Yao received honoraria and research funding from Novartis. The study was designed under the responsibility of Novartis Pharmaceutical Corporation, in conjunction with the steering committee. The study was funded by Novartis Pharmaceutical Corporation. Everolimus was provided by Novartis Pharmaceutical Corporation. Novartis Pharmaceutical Corporation collected and analyzed the data and contributed to the interpretation of the study. All authors had full access to all of the data in the study and had final responsibility for the decision to submit for publication. Roberto Buzzoni, Edward Wolin, Paola Tomassetti, Jiri Tomasek, and Matthew H. Kulke have no conflict of interest. References: Yao, J.C., Hassan, M., Phan, A., One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States (2008) J Clin Oncol, 26, pp. 3063-3072; Detterbeck, F.C., Clinical presentation and evaluation of neuroendocrine tumors of the lung (2014) Thorac Surg Clin, 24, pp. 267-276; Taal, B.G., Visser, O., Epidemiology of neuroendocrine tumours (2004) Neuroendocrinology, 80, pp. 3-7; Rekhtman, N., Neuroendocrine tumors of the lung: an update (2010) Arch Pathol Lab Med, 134, pp. 1628-1638; Oberg, K., Hellman, P., Ferolla, P., Papotti, M., Group, E.G.W., Neuroendocrine bronchial and thymic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2012) Ann Oncol, 23, pp. vii120-vii123; Granberg, D., Neuroendocrine tumors of the lung (2015) Neuroendocrine Tumors: Diagnosis and Management, pp. 143-164. , In, Yalcin S, {\"O}berg K, eds., Berlin, Heidelberg, Springer-Verlag; Filosso, P.L., Ferolla, P., Guerrera, F., Multidisciplinary management of advanced lung neuroendocrine tumors (2015) J Thorac Dis, 7, pp. S163-S171; Krug, L.M., Kris, M.G., Rosenzweig, K., Cancer of the Lung: small cell and other neuroendocrine tumors of the lung (2008) Cancer Principles and Practice of Oncology, pp. 946-971. , In, DeVita VT, Lawrence TS, Rosenberg SA, Weinberg RA, Depinho RA, eds., Alphen aan den Rijn, Wolters Kluwer, Lippincott Williams and Wilkins; Pavel, M., O'Toole, D., Costa, F., ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site (2016) Neuroendocrinology, 103, pp. 172-185; Filosso, P.L., Ruffini, E., Oliaro, A., Papalia, E., Donati, G., Rena, O., Long-term survival of atypical bronchial carcinoids with liver metastases, treated with octreotide (2002) Eur J Cardiothorac Surg, 21, pp. 913-917; Waldherr, C., Pless, M., Maecke, H.R., Haldemann, A., Mueller-Brand, J., The clinical value of [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: a clinical phase II study (2001) Ann Oncol, 12, pp. 941-945; Mariniello, A., Bodei, L., Tinelli, C., Long-term results of PRRT in advanced bronchopulmonary carcinoid (2016) Eur J Nucl Med Mol Imaging, 43, pp. 441-452; Kulke, M.H., Lenz, H.J., Meropol, N.J., Activity of sunitinib in patients with advanced neuroendocrine tumors (2008) J Clin Oncol, 26, pp. 3403-3410; Grande, E., Capdevila, J., Castellano, D., Pazopanib in pretreated advanced neuroendocrine tumors: a phase II, open-label trial of the Spanish Task Force Group for Neuroendocrine Tumors (GETNE) (2015) Ann Oncol, 26, pp. 1987-1993; Yao, J.C., Phan, A., Hoff, P.M., Targeting vascular endothelial growth factor in advanced carcinoid tumor: a random assignment phase II study of depot octreotide with bevacizumab and pegylated interferon alpha-2b (2008) J Clin Oncol, 26, pp. 1316-1323; Brizzi, M.P., Berruti, A., Ferrero, A., Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte oncology network (2009) BMC Cancer, 9, p. 388; Bajetta, E., Catena, L., Procopio, G., Are capecitabine and oxaliplatin (XELOX) suitable treatments for progressing low-grade and high-grade neuroendocrine tumours? (2007) Cancer Chemother Pharmacol, 59, pp. 637-642; Ekeblad, S., Sundin, A., Janson, E.T., Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors (2007) Clin Cancer Res, 13, pp. 2986-2991; Fazio, N., Granberg, D., Grossman, A., Everolimus plus octreotide long-acting repeatable in patients with advanced lung neuroendocrine tumors: analysis of the phase 3, randomized, placebo-controlled RADIANT-2 study (2013) Chest, 143, pp. 955-962; Yao, J.C., Lombard-Bohas, C., Baudin, E., Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial (2010) J Clin Oncol, 28, pp. 69-76; Yao, J.C., Shah, M.H., Ito, T., Everolimus for advanced pancreatic neuroendocrine tumors (2011) N Engl J Med, 364, pp. 514-523; Yao, J.C., Fazio, N., Singh, S., Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study (2016) Lancet, 387, pp. 968-977; Klimstra, D.S., Modlin, I.R., Coppola, D., Lloyd, R.V., Suster, S., The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems (2010) Pancreas, 39, pp. 707-712; Rindi, G., Arnold, R., Bosman, F.T., Nomenclature and classification of neuroendocrine neoplasm of the digestive system (2010) WHO Classification of Tumours of the Digestive System, pp. 13-14. , In, Bosman FT, Carniero F, Hruban RH, Theise ND, eds., 4th edn, Lyon, International Agency for Research on Cancer; Hendifar, A.E., Marchevsky, A.M., Tuli, R., Neuroendocrine tumors of the lung: current challenges and advances in the diagnosis and management of well-differentiated disease (2017) J Thorac Oncol, 12, pp. 425-436; Pelosi, G.F.A., Cossa, M., What clinicians are asking pathologists when dealing with lung neuroendocrine neoplasms? (2015) Semin Diagn Pathol, 32, pp. 469-479; Ferolla, P., Brizzi, M.P., Meyer, T., 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 (2016) Ann Oncol, 27, pp. 136-148; Yao, J.C., Fazio, N., Singh, S., Everolimus (EVE) in advanced, nonfunctional, well-differentiated neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin: second interim overall survival (OS) results from the RADIANT-4 study (2016) J Clin Oncol, 34, p. 4090",
year = "2018",
doi = "10.1111/cas.13427",
language = "English",
volume = "109",
pages = "174--181",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "1",

}

TY - JOUR

T1 - Everolimus in advanced, progressive, well-differentiated, non-functional neuroendocrine tumors: RADIANT-4 lung subgroup analysis

AU - Fazio, N.

AU - Buzzoni, R.

AU - Delle Fave, G.

AU - Tesselaar, M.E.

AU - Wolin, E.

AU - Van Cutsem, E.

AU - Tomassetti, P.

AU - Strosberg, J.

AU - Voi, M.

AU - Bubuteishvili-Pacaud, L.

AU - Ridolfi, A.

AU - Herbst, F.

AU - Tomasek, J.

AU - Singh, S.

AU - Pavel, M.

AU - Kulke, M.H.

AU - Valle, J.W.

AU - Yao, J.C.

N1 - Cited By :2 Export Date: 5 February 2019 CODEN: CSACC Correspondence Address: Fazio, N.; European Institute of Oncology, IRCCSItaly; email: nicola.fazio@ieo.it Chemicals/CAS: everolimus, 159351-69-6; Antineoplastic Agents; Everolimus Funding details: European Society for Medical Oncology, ESMO Funding details: Bayer Funding details: Novartis Funding details: Ipsen Fund Funding details: Boehringer Ingelheim Funding details: Sanofi Funding details: Pfizer Funding details: Novartis Pharmaceuticals Corporation, NPC Funding text 1: This research was presented in part at the Annual European Neuroendocrine Tumors Society (ENETS) Conference, March 9-11, 2016 in Barcelona, Spain and the European Society of Medical Oncology (ESMO) Congress, October 7-11, 2016, Copenhagen, Denmark. Funding text 2: Nicola Fazio received honoraria from Novartis, Ipsen, and Pfizer, and his institution received research funding from Novartis and Merck Serono. Gianfranco Delle Fave received honoraria and research funding from Novartis. Margot Tesselaar received research funding from Novartis. Eric Van Cutsem received research funding from Novartis, Ipsen, Sanofi, Roche, Bayer, and Boehringer. Jonathan Strosberg received research funding from Novartis and Ipsen and his institution received research funding from Novartis. Maurizio Voi and Fabian Herbst are employees of Novartis and have stock ownership from Novartis. Lida Bubuteishvili-Pacaud and Antonia Ridolfi are employees of Novartis. Simron Singh received research funding from Novartis. Marianne Pavel received honoraria from Novartis and her institution received research funding from Novartis. Juan W. Valle received honoraria and travel reimbursement from Novartis, and his institution received research funding from Novartis. James C. Yao received honoraria and research funding from Novartis. The study was designed under the responsibility of Novartis Pharmaceutical Corporation, in conjunction with the steering committee. The study was funded by Novartis Pharmaceutical Corporation. Everolimus was provided by Novartis Pharmaceutical Corporation. Novartis Pharmaceutical Corporation collected and analyzed the data and contributed to the interpretation of the study. All authors had full access to all of the data in the study and had final responsibility for the decision to submit for publication. Roberto Buzzoni, Edward Wolin, Paola Tomassetti, Jiri Tomasek, and Matthew H. Kulke have no conflict of interest. References: Yao, J.C., Hassan, M., Phan, A., One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States (2008) J Clin Oncol, 26, pp. 3063-3072; Detterbeck, F.C., Clinical presentation and evaluation of neuroendocrine tumors of the lung (2014) Thorac Surg Clin, 24, pp. 267-276; Taal, B.G., Visser, O., Epidemiology of neuroendocrine tumours (2004) Neuroendocrinology, 80, pp. 3-7; Rekhtman, N., Neuroendocrine tumors of the lung: an update (2010) Arch Pathol Lab Med, 134, pp. 1628-1638; Oberg, K., Hellman, P., Ferolla, P., Papotti, M., Group, E.G.W., Neuroendocrine bronchial and thymic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2012) Ann Oncol, 23, pp. vii120-vii123; Granberg, D., Neuroendocrine tumors of the lung (2015) Neuroendocrine Tumors: Diagnosis and Management, pp. 143-164. , In, Yalcin S, Öberg K, eds., Berlin, Heidelberg, Springer-Verlag; Filosso, P.L., Ferolla, P., Guerrera, F., Multidisciplinary management of advanced lung neuroendocrine tumors (2015) J Thorac Dis, 7, pp. S163-S171; Krug, L.M., Kris, M.G., Rosenzweig, K., Cancer of the Lung: small cell and other neuroendocrine tumors of the lung (2008) Cancer Principles and Practice of Oncology, pp. 946-971. , In, DeVita VT, Lawrence TS, Rosenberg SA, Weinberg RA, Depinho RA, eds., Alphen aan den Rijn, Wolters Kluwer, Lippincott Williams and Wilkins; Pavel, M., O'Toole, D., Costa, F., ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site (2016) Neuroendocrinology, 103, pp. 172-185; Filosso, P.L., Ruffini, E., Oliaro, A., Papalia, E., Donati, G., Rena, O., Long-term survival of atypical bronchial carcinoids with liver metastases, treated with octreotide (2002) Eur J Cardiothorac Surg, 21, pp. 913-917; Waldherr, C., Pless, M., Maecke, H.R., Haldemann, A., Mueller-Brand, J., The clinical value of [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: a clinical phase II study (2001) Ann Oncol, 12, pp. 941-945; Mariniello, A., Bodei, L., Tinelli, C., Long-term results of PRRT in advanced bronchopulmonary carcinoid (2016) Eur J Nucl Med Mol Imaging, 43, pp. 441-452; Kulke, M.H., Lenz, H.J., Meropol, N.J., Activity of sunitinib in patients with advanced neuroendocrine tumors (2008) J Clin Oncol, 26, pp. 3403-3410; Grande, E., Capdevila, J., Castellano, D., Pazopanib in pretreated advanced neuroendocrine tumors: a phase II, open-label trial of the Spanish Task Force Group for Neuroendocrine Tumors (GETNE) (2015) Ann Oncol, 26, pp. 1987-1993; Yao, J.C., Phan, A., Hoff, P.M., Targeting vascular endothelial growth factor in advanced carcinoid tumor: a random assignment phase II study of depot octreotide with bevacizumab and pegylated interferon alpha-2b (2008) J Clin Oncol, 26, pp. 1316-1323; Brizzi, M.P., Berruti, A., Ferrero, A., Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte oncology network (2009) BMC Cancer, 9, p. 388; Bajetta, E., Catena, L., Procopio, G., Are capecitabine and oxaliplatin (XELOX) suitable treatments for progressing low-grade and high-grade neuroendocrine tumours? (2007) Cancer Chemother Pharmacol, 59, pp. 637-642; Ekeblad, S., Sundin, A., Janson, E.T., Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors (2007) Clin Cancer Res, 13, pp. 2986-2991; Fazio, N., Granberg, D., Grossman, A., Everolimus plus octreotide long-acting repeatable in patients with advanced lung neuroendocrine tumors: analysis of the phase 3, randomized, placebo-controlled RADIANT-2 study (2013) Chest, 143, pp. 955-962; Yao, J.C., Lombard-Bohas, C., Baudin, E., Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial (2010) J Clin Oncol, 28, pp. 69-76; Yao, J.C., Shah, M.H., Ito, T., Everolimus for advanced pancreatic neuroendocrine tumors (2011) N Engl J Med, 364, pp. 514-523; Yao, J.C., Fazio, N., Singh, S., Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study (2016) Lancet, 387, pp. 968-977; Klimstra, D.S., Modlin, I.R., Coppola, D., Lloyd, R.V., Suster, S., The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems (2010) Pancreas, 39, pp. 707-712; Rindi, G., Arnold, R., Bosman, F.T., Nomenclature and classification of neuroendocrine neoplasm of the digestive system (2010) WHO Classification of Tumours of the Digestive System, pp. 13-14. , In, Bosman FT, Carniero F, Hruban RH, Theise ND, eds., 4th edn, Lyon, International Agency for Research on Cancer; Hendifar, A.E., Marchevsky, A.M., Tuli, R., Neuroendocrine tumors of the lung: current challenges and advances in the diagnosis and management of well-differentiated disease (2017) J Thorac Oncol, 12, pp. 425-436; Pelosi, G.F.A., Cossa, M., What clinicians are asking pathologists when dealing with lung neuroendocrine neoplasms? (2015) Semin Diagn Pathol, 32, pp. 469-479; Ferolla, P., Brizzi, M.P., Meyer, T., 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 (2016) Ann Oncol, 27, pp. 136-148; Yao, J.C., Fazio, N., Singh, S., Everolimus (EVE) in advanced, nonfunctional, well-differentiated neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin: second interim overall survival (OS) results from the RADIANT-4 study (2016) J Clin Oncol, 34, p. 4090

PY - 2018

Y1 - 2018

N2 - 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

AB - 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

KW - everolimus

KW - lung carcinoid

KW - neuroendocrine tumors

KW - progression-free survival

KW - RADIANT-4

KW - antineoplastic agent

KW - adult

KW - advanced cancer

KW - aged

KW - anemia

KW - aphthous stomatitis

KW - Article

KW - asthenia

KW - body weight loss

KW - cancer chemotherapy

KW - cancer regression

KW - cancer survival

KW - clinical outcome

KW - cohort analysis

KW - controlled study

KW - coughing

KW - decreased appetite

KW - diarrhea

KW - drug efficacy

KW - drug safety

KW - dysgeusia

KW - dyspnea

KW - exploratory research

KW - fatigue

KW - female

KW - fever

KW - glossitis

KW - human

KW - hyperglycemia

KW - infection

KW - lung cancer

KW - major clinical study

KW - male

KW - median survival time

KW - mouth ulcer

KW - multicenter study (topic)

KW - nausea

KW - neuroendocrine tumor

KW - peripheral edema

KW - phase 3 clinical trial (topic)

KW - pneumonia

KW - post hoc analysis

KW - priority journal

KW - progression free survival

KW - pruritus

KW - randomized controlled trial (topic)

KW - rash

KW - side effect

KW - stomatitis

KW - treatment response

KW - xerostomia

KW - clinical trial

KW - disease free survival

KW - double blind procedure

KW - lung tumor

KW - middle aged

KW - multicenter study

KW - phase 3 clinical trial

KW - prospective study

KW - randomized controlled trial

KW - treatment outcome

KW - very elderly

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Agents

KW - Disease-Free Survival

KW - Double-Blind Method

KW - Everolimus

KW - Female

KW - Humans

KW - Lung Neoplasms

KW - Male

KW - Middle Aged

KW - Neuroendocrine Tumors

KW - Prospective Studies

KW - Treatment Outcome

U2 - 10.1111/cas.13427

DO - 10.1111/cas.13427

M3 - Article

VL - 109

SP - 174

EP - 181

JO - Cancer Science

JF - Cancer Science

SN - 1347-9032

IS - 1

ER -