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Clinical Trial
. 2023 Dec;129(12):1930-1939.
doi: 10.1038/s41416-023-02462-0. Epub 2023 Oct 23.

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

Siren Morken  1 , Seppo W Langer  2   3 , Anna Sundlöv  4 , Lene Weber Vestermark  5 , Morten Ladekarl  6   7   8 , Geir Olav Hjortland  9 , Johanna B Svensson  10 , Elizaveta Mitkina Tabaksblat  6 , Torjan Magne Haslerud  11 , Jörg Assmus  12 , Sönke Detlefsen  13   14 , Anne Couvelard  15 , Aurel Perren  16 , Halfdan Sorbye  17   18
Affiliations
Clinical Trial

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

Siren Morken et al. Br J Cancer. 2023 Dec.

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%, 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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Conflict of interest statement

HS: Consultant/advisory board: Hutchison, Bayer, ITM, AAA. Lecture Honoraria; Novartis, Ipsen, Bayer, SAM Nordic, Pierre Fabre. ML: Unrestricted research grant from Scandion Oncology A/S.

Figures

Fig. 1
Fig. 1. Response and survival in 37 HG GEP-NEN patients receiving first-line treatment with everolimus/temozolomide.
Waterfall-plot (a) showing treatment response for all patients, the maximum change in the sum of the target lesion. Kaplan–Meier curves showing median progression-free (b) and median overall (c) survival for all patients and for the NET G3 and NEC sub-groups.
Fig. 2
Fig. 2. Toxicity reported under first-line treatment with everolimus/temozolomide.
The stacked bar chart showing the safety profile according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Fig. 3
Fig. 3. Quality of life (QoL) under first-line treatment with everolimus/temozolomide.
Forest-plot describing changes in the QoL according to the European Organization for Research and Treatment of Cancer QoL questionnaire (EORTC QLQ-C30).
See this image and copyright information in PMC

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