In a French phase II trial (MGMT-NET) reported in the Journal of Clinical Oncology, Walter et al found evidence of activity of alkylating agent–based therapy among patients who have neuroendocrine tumors (NETs) with MGMT-deficient (dMGMT) status.
Study Details
In the multicenter open-label trial, 105 patients were randomly assigned between October 2018 and October 2021 to alkylating agent–based (n = 62) or oxaliplatin-based treatment (n = 43) in a 1:1 ratio for patients with MGMT proficient (pMGMT) status and in a 2:1 ratio for patients with dMGMT status. The primary outcome measure was objective response rate at 3 months with alkylating agent treatment of dMGMT vs pMGMT disease, with a criterion of a 35% difference in response rates favoring dMGMT used to determine significant benefit.
Key Findings
Among 102 patients with interpretable MGMT status, 58 (56.9%) had dMGMT status. The primary endpoint was not reached: with alkylating agent–based treatment, the 3-month objective response rate was 29.4% in the dMGMT group vs 8.0% in the pMGMT group (odds ratio = 3.5, 95% confidence interval [CI] = 0.58–21.16, P = .172). Best objective response rate (52.9% vs 11.5%) and median progression-free survival (14.6 months, 95% CI = 7.2–22.1 months, vs 11.3 months, 95% CI = 9.4–13.2 months) were better in patients with dMGMT vs pMGMT status.
MGMT status did not appear to affect the activity of oxaliplatin-based treatment. In the dMGMT group, the best objective response rate was 52.9% with alkylating agent–based vs 25.0% with oxaliplatin-based treatment (P = .031), with a borderline significant difference observed in progression-free survival (HR = 0.56, 95% CI = 0.31–1.01, P = .053). In the pMGMT group, the best objective response rate was 11.5% with alkylating agent–based treatment vs 38.9% with oxaliplatin-based treatment (P = .040), with no significant difference in progression-free survival being observed (HR = 1.12, 95% CI = 0.06–2.10, P = .716).
The investigators concluded: “Despite the fact that the primary end point was not reached, [alkylating agents have] clinical activity in patients with dMGMT-NETs.”
Thomas Walter, MD, PhD, of Edouard Herriot Hospital, Hospices Civils de Lyon, France, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by the French Ministry of Health. For full disclosures of the study authors, visit ascopubs.org.
