TY - JOUR

T1 - Phase II study of everolimus and temozolomide as first-line treatment in metastatic high-grade gastroenteropancreatic neuroendocrine neoplasms

AU - Morken, Siren

AU - Langer, Seppo W

AU - Sundlöv, Anna

AU - Vestermark, Lene Weber

AU - Ladekarl, Morten

AU - Hjortland, Geir Olav

AU - Svensson, Johanna B

AU - Tabaksblat, Elizaveta Mitkina

AU - Haslerud, Torjan Magne

AU - Assmus, Jörg

AU - Detlefsen, Sönke

AU - Couvelard, Anne

AU - Perren, Aurel

AU - Sorbye, Halfdan

N1 - © 2023. The Author(s).

PY - 2023

Y1 - 2023

N2 - 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 2 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).

AB - 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 2 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).

U2 - 10.1038/s41416-023-02462-0

DO - 10.1038/s41416-023-02462-0

M3 - Journal article

C2 - 37872405

VL - 129

SP - 1930

EP - 1939

JO - The British journal of cancer. Supplement

JF - The British journal of cancer. Supplement

SN - 0007-0920

ER -