Combined data from two phase 2 trials indicate that avelumab monotherapy had limited antitumor activity in patients with grade 2/3 neuroendocrine neoplasms (NENs).
To assess the role of immunotherapy in NENs, the phase 2 NET-001 (NCT03278405) and NET-002 trials (NCT03278379) were initiated to investigate the efficacy and safety of the anti–programmed cell death ligand 1 inhibitor avelumab. NET-001 completed accrual of 10 patients; the NET-002 trial, with a planned enrollment of 36 patients, was terminated at its interim analysis because of lack of efficacy. The results of the combined patient cohort enrolled in both trials were reported at the 2020 North American Neuroendocrine Tumor Society Annual Symposium.
Eligibility criteria included patients with unresectable or metastatic World Health Organization grade 2/3 NENs from a gastroenteropancreatic (GEP) or lung primary, ≤2 prior lines of therapy excluding somatostatin analogs, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2. NET-001 investigated grade 3 poorly differentiated GEP neuroendocrine carcinomas, and NET-002 investigated grade 2/3 well-differentiated GEP neuroendocrine tumors. In both trials, eligible patients received avelumab 10 mg/kg intravenously every 2 weeks for 26 cycles. The primary end point was overall response rate by Response Evaluation Criteria in Solid Tumors version 1.1; secondary end points included progression-free survival (PFS), overall survival (OS), disease control rate (DCR) at 6 months, and toxicity.
In the combined cohort, a total of 27 patients were included, of which 10 patients were enrolled in the NET-001 trial and 17 patients in the NET-002 trial. Of the 27 tumors, 21 were GEP and 6 had lung origin. The median age of the combined cohort was 64 years (range, 37-80 years), 30% of patients had ECOG PS 1 to 2, and 78% of patients had received ≤1 prior lines of therapy. The median Ki67 index was 35% (range, 10%-100%). The median time on treatment was 85 days (7 cycles).
In the 24 patients evaluable for efficacy, no objective responses were achieved; stable disease was achieved in 33% of patients, and 6-month DCR was 21%. The median PFS was 3.3 months (range, 1.2-24.6 months), and median OS was 14.2 months.
In the 25 patients who received ≥1 doses of avelumab and were evaluable for safety, treatment-related adverse events (TRAEs; all grades) occurred in 58% of patients. Three patients had grade 3/4 TRAEs leading to treatment discontinuation, 2 patients with hepatitis and 1 patient with infusion-related reaction.
Based on these results, immunotherapy with single-agent avelumab was associated with limited antitumor activity in patients with grade 2/3 NENs; further studies are needed to evaluate the role of dual immunotherapy or combination with chemotherapy in this patient population.
Source: Chan D, et al. North American Neuroendocrine Tumor Society 2020 Annual Symposium; October 1-3, 2020. Abstract C18.