Results of a placebo-controlled, randomized phase 2 trial indicate that maintenance treatment with lanreotide autogel (LAN) following first-line treatment may provide clinical benefit in aggressive grade 1 and 2, well-differentiated, duodeno-pancreatic neuroendocrine tumors (NETs).
Systemic chemotherapy is the standard of care for patients with aggressive metastatic or locally advanced, nonresectable, grade 1 to 2 well-differentiated duodeno-pancreatic NETs until progression. REMINET is an international, double-blind, placebo-controlled, randomized phase 2 trial that evaluated the safety and efficacy of LAN as maintenance treatment after first-line chemotherapy in patients with aggressive grade 1 and 2 well-differentiated duodeno-pancreatic NETs; study results were reported at the European Society for Medical Oncology Virtual Congress 2020.
Eligible patients were randomized in a 1:1 ratio to receive LAN 120 mg or placebo every 28 days until progression and/or toxicity. Stratification was by center, grade (1 vs 2), degree of liver involvement (≤25% vs >25%), metastases (locoregional vs hepatic only vs hepatic + others), pretreatment analogs (Ki67 <10% vs >10), and type of first-line treatment. The primary end point was the rate of patients alive without progression at 6 months.
A total of 53 patients were enrolled; the median age of the study cohort was 66 years, 81% had a grade 2 tumor, and 90.6% had metastatic disease, including 25.1% with ≥2 metastatic sites. The percentage of patients who had previously received somatostatin analogs was 14.8% in the LAN group and 19.2% in the placebo group. The majority of patients had received first-line chemotherapy (96.2%), which was primarily temozolomide-based (52.9%), dacarbazine-based (18.7%), streptozotocin-based (13.3%), or oxaliplatin-based (11.3%); 3.8% of patients received first-line sunitinib. At randomization, partial response was achieved by 18.9% of patients and stable disease by 81.1%.
With a median follow-up of 27.0 months (95% confidence interval [CI], 19.5-31.2), the 6-month progression-free survival (PFS) rate in the LAN group was 73.1% (90% CI, 55.3-86.6) compared with 54.2% (90% CI, 35.8-71.8) in the placebo group; the median PFS was 19.4 months (95% CI, 7.6-32.6) and 7.6 months (95% CI, 3.0-9.0), respectively. Duration of disease control was longer in the LAN group (median, 46.9 months; 95% CI, 29.3-not estimable [NE]) compared with the placebo group (median, 28.2 months; 95% CI, 18.9-NE). The median overall survival was not reached in the LAN group and was 41.9 months (95% CI, 38.7-NE) in the placebo group.
The majority of treatment-related adverse events (TRAEs) in the LAN group were grade 2 (74.1%); grade 3 adverse events (AEs) occurred in 9 (33.3%) patients versus 5 (20.0%) patients in the placebo group. Serious AEs were reported in 5 (18.5%) patients. The most common TRAEs (any grade) were diarrhea (74.1% vs 28.0%), abdominal pain (48.1% vs 36.0%), nausea (25.9% vs 16.0%), vomiting (14.8% vs 4.0%), fatigue (29.6% vs 28.0%), and hyperglycemia (18.5% vs 16.0%).
These results suggest that maintenance treatment with LAN following first-line treatment may provide clinical benefit in aggressive grade 1 and 2, well-differentiated, duodeno-pancreatic NETs, and warrants further evaluation.
Source: Lepage PJ, et al. Ann Oncol. 2020;31(suppl 4). Abstract 1163P.
