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Phase II study of everolimus and temozolomide as first-line treatment in metastatic high-grade gastroenteropancreatic neuroendocrine neoplasms

Morken, Siren ; Langer, Seppo W. ; Sundlöv, Anna LU orcid ; Vestermark, Lene Weber ; Ladekarl, Morten ; Hjortland, Geir Olav ; Svensson, Johanna B. ; Tabaksblat, Elizaveta Mitkina ; Haslerud, Torjan Magne and Assmus, Jörg , et al. (2023) In British Journal of Cancer 129(12). p.1930-1939
Abstract

Background: The optimal treatment for metastatic high-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms when Ki-67 ≤55% is unknown. A prospective multi-centre phase 2 study was performed to evaluate the efficacy and safety of everolimus and temozolomide as first-line treatment for these patients. Methods: Patients received everolimus 10 mg daily continuously and temozolomide 150 mg/m2 for 7 days every 2 weeks. Endpoints included response, survival, safety and quality of life (QoL). Histopathological re-evaluation according to the 2019 WHO classification was performed. Results: For 37 eligible patients, the primary endpoint with 65% disease control rate (DCR) at 6 months (m) was reached. The response rate was 30%,... (More)

Background: The optimal treatment for metastatic high-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms when Ki-67 ≤55% is unknown. A prospective multi-centre phase 2 study was performed to evaluate the efficacy and safety of everolimus and temozolomide as first-line treatment for these patients. Methods: Patients received everolimus 10 mg daily continuously and temozolomide 150 mg/m2 for 7 days every 2 weeks. Endpoints included response, survival, safety and quality of life (QoL). Histopathological re-evaluation according to the 2019 WHO classification was performed. Results: For 37 eligible patients, the primary endpoint with 65% disease control rate (DCR) at 6 months (m) was reached. The response rate was 30%, the median progression-free survival (PFS) 10.2 months and the median overall survival (OS) 26.4 months. Considering 26 NET G3 patients, 6 months DCR was 77% vs. 22% among nine NEC patients (p = 0.006). PFS was superior for NET G3 vs. NEC (12.6 months vs. 3.4 months, Log-rank-test: p = 0.133, Breslow-test: p < 0.001). OS was significantly better for NET G3 (31.4 months vs. 7.8 months, p = 0.003). Grade 3 and 4 toxicities were reported in 43% and 38%. QoL remained stable during treatment. Conclusion: Everolimus and temozolomide may be a treatment option for selected GEP-NET G3 patients including careful monitoring. Toxicity did not compromise QoL. Clinical trial registration: ClinicalTrials.gov (NTC02248012).

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publishing date
type
Contribution to journal
publication status
published
subject
in
British Journal of Cancer
volume
129
issue
12
pages
10 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:37872405
  • scopus:85174609831
ISSN
0007-0920
DOI
10.1038/s41416-023-02462-0
language
English
LU publication?
yes
id
73d1b48e-5365-40a2-962c-10beefd44096
date added to LUP
2023-12-18 13:24:13
date last changed
2024-04-17 01:31:42
@article{73d1b48e-5365-40a2-962c-10beefd44096,
  abstract     = {{<p>Background: The optimal treatment for metastatic high-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms when Ki-67 ≤55% is unknown. A prospective multi-centre phase 2 study was performed to evaluate the efficacy and safety of everolimus and temozolomide as first-line treatment for these patients. Methods: Patients received everolimus 10 mg daily continuously and temozolomide 150 mg/m<sup>2</sup> for 7 days every 2 weeks. Endpoints included response, survival, safety and quality of life (QoL). Histopathological re-evaluation according to the 2019 WHO classification was performed. Results: For 37 eligible patients, the primary endpoint with 65% disease control rate (DCR) at 6 months (m) was reached. The response rate was 30%, the median progression-free survival (PFS) 10.2 months and the median overall survival (OS) 26.4 months. Considering 26 NET G3 patients, 6 months DCR was 77% vs. 22% among nine NEC patients (p = 0.006). PFS was superior for NET G3 vs. NEC (12.6 months vs. 3.4 months, Log-rank-test: p = 0.133, Breslow-test: p &lt; 0.001). OS was significantly better for NET G3 (31.4 months vs. 7.8 months, p = 0.003). Grade 3 and 4 toxicities were reported in 43% and 38%. QoL remained stable during treatment. Conclusion: Everolimus and temozolomide may be a treatment option for selected GEP-NET G3 patients including careful monitoring. Toxicity did not compromise QoL. Clinical trial registration: ClinicalTrials.gov (NTC02248012).</p>}},
  author       = {{Morken, Siren and Langer, Seppo W. and Sundlöv, Anna and Vestermark, Lene Weber and Ladekarl, Morten and Hjortland, Geir Olav and Svensson, Johanna B. and Tabaksblat, Elizaveta Mitkina and Haslerud, Torjan Magne and Assmus, Jörg and Detlefsen, Sönke and Couvelard, Anne and Perren, Aurel and Sorbye, Halfdan}},
  issn         = {{0007-0920}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{1930--1939}},
  publisher    = {{Nature Publishing Group}},
  series       = {{British Journal of Cancer}},
  title        = {{Phase II study of everolimus and temozolomide as first-line treatment in metastatic high-grade gastroenteropancreatic neuroendocrine neoplasms}},
  url          = {{http://dx.doi.org/10.1038/s41416-023-02462-0}},
  doi          = {{10.1038/s41416-023-02462-0}},
  volume       = {{129}},
  year         = {{2023}},
}