LBA54 - Alkylating agent-based vs oxaliplatin-based chemotherapy in neuroendocrine tumours according to the O6-methylguanine-DNA methyltransferase (MGMT) status: A randomized phase II study (MGMT-NET) on behalf of the French Group of Endocrine Tumors (GTE) and ENDOCAN-RENATEN network

Background

Alkylating agents (ALKY, temozolomide, darcabazine and streptozotocin), and oxaliplatin (Ox) are the main chemotherapies used for advanced neuroendocrine tumours (NETs). O⁶-Methylguanine-DNA methyltransferase (MGMT) status, as proficient (p) or deficient (d), may be a predictor of response to ALKY.

Methods

MGMT-NET (NCT03217097) is a randomized phase 2 trial. Main inclusion criteria were confirmed advanced pancreatic, thoracic, or unknown (Uk) primary NETs with an indication for chemotherapy and tissue available. The primary aim was to demonstrate an improvement of the objective response rate (ORR) assessed by RECIST-v1.1 at 3 months from 15% in pMGMT NETs to 50% in dMGMT NETs with ALKY. Secondary aims were the best ORR, progression-free-survival (PFS) and overall survival (OS) of ALKY; oxaliplatin-based chemotherapy (Ox) serves as an internal-control. For the primary aim, dMGMT was defined using pyrosequencing if the MGMT was methylated (> 8%) and using immunochemistry if MGMT expression was lost (H-score<50) when pyrosequencing was not available.

Results

From Oct 2018 to Oct 2021, 105 patients (55 pancreas, 38 thoracic, 12 Uk) started either ALKY (n=62) or Ox (n=43, 1:1 for pMGMT or 2:1 for dMGMT NETs). Median age was 63 years (range 30–84), 57% males, NET were G1 (28%), G2 (60%) or G3 (10%). 102 had MGMT status available, 39/91 (43%) and 39/82 (48%) were dMGMT when assessed by pyrosequencing or immunohistochemistry, respectively. The primary aim was not met but best ORR, PFS and OS were greater in ALKY-dMGMT group (Table). Results will be also given by technique of MGMT evaluation during the meeting. Table: LBA54

Conclusions

ALKY provides a higher response rate for dMGMT-NET while Ox chemotherapy may be a better option in pMGMT-NET.

Clinical trial identification

NCT03217097.

Editorial acknowledgement

Legal entity responsible for the study

Hospices Civils de Lyon.

Funding

Supported by Clinical Research Hospital Program grants (PHRC 2016) from the French ministry of health (PHRCK-16-0208).

Disclosure

T. Walter: Financial Interests, Personal, Invited Speaker: Novartis-AAA; Non-Financial Interests, Personal, Invited Speaker: IPSEN; Non-Financial Interests, Institutional, Funding: Roche. T. Lecomte: Financial Interests, Personal, Advisory Board: Ipsen, Pierre Fabre, Servier, Amgen, Dicephera, AAA Novartis, Merck Serono; Financial Interests, Institutional, Local PI: AstraZeneca, Mirati, ALX oncology; Financial Interests, Institutional, Funding: LeoPharma, Pierre Fabre. J. Hadoux: Financial Interests, Personal, Advisory Board: IPSEN, AAA, Roche, PharmaMar, lilly; Financial Interests, Personal, Research Funding: Novartis. V. Hautefeuille: Non-Financial Interests, Personal, Other: novartis; Non-Financial Interests, Personal, Invited Speaker: AAA; Non-Financial Interests, Personal, Advisory Board: Amgen; Non-Financial Interests, Personal, Principal Investigator: Ipsen. C. Do Cao: Non-Financial Interests, Personal, Invited Speaker: Ipsen, Novartis. T. Aparicio: Financial Interests, Personal, Advisory Board: Bioven, Servier, Sirtec; Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, Pierre Fabre; Financial Interests, Personal, Expert Testimony: MSD. C. Lombard Bohas: Financial Interests, Institutional, Principal Investigator: Ipsen; Financial Interests, Personal, Advisory Board: AAA. All other authors have declared no conflicts of interest.