Highlights
- •There are few treatments for high-grade advanced neuroendocrine neoplasms (NENs).
- •We treated 27 patients with advanced NENs with avelumab, a PD-L1-directed antibody.
- •No objective responses were observed; stable disease was achieved in 33% of patients.
Abstract
Background
Higher grade neuroendocrine neoplasm (NENs) continues to pose a treatment dilemma,
with the optimal treatment undefined. Although immunotherapy has revolutionised the
treatment of many cancers, its role in NENs remains unclear. We aimed to investigate
the efficacy and safety of avelumab, a PD-L1-directed antibody, in patients with advanced
unresectable/metastatic higher grade NENs.
Methods
NET001 and NET002 are phase II studies investigating avelumab (NCT03278405 and NCT03278379).
Eligible patients had unresectable and/or metastatic WHO G2-3 NENs from a gastroenteropancreatic
(GEP) source or a bronchial primary (excluding typical carcinoid) and 0–2 prior lines
of systemic therapy (excluding SSAs). Patients were treated with avelumab 10 mg/kg
intravenously every two weeks for 26 cycles. NET001 investigated G3 poorly differentiated
GEP neuroendocrine carcinomas (NECs) and bronchial small/large cell NEC, whereas NET002
investigated G2-3 well-differentiated GEPNETs and bronchial atypical carcinoids. The
primary endpoint in both trials was overall response rate (ORR) by RECIST v1.1; secondary
endpoints included progression-free survival, overall survival, disease control rate
at six months and toxicity.
Results
Twenty-seven patients were enrolled (21 GEP, 6 lung; 10 in NET-001, 17 in NET-002);
median age 64 (range 37–80), 30% ECOG PS 1–2 and 78% received 1+ lines of prior therapy.
The median Ki-67 index was 35% (range 10–100). Twelve of the twenty-seven patients
had died at the time of data lock. The median time on treatment was 85 days (seven
cycles). No objective responses were observed. Stable disease was achieved in 33%
of patients, and the disease control rate at 6 mo was 21%. The median PFS was 3.3
months (range 1.2–24.6), and the median OS was 14.2 months. Treatment-related adverse
events (all grades) occurred in 58% of patients. Three patients had treatment-related
grade 3–4 AEs leading to treatment discontinuation (immune-related hepatitis n = 2
and infusion-related reaction n = 1).
Conclusion
Single-agent PD-L1 blockade with avelumab showed limited antitumour activity in patients
with G2-3 NENs. Correlative studies are underway. Further studies are needed to explore
the role of dual immunotherapy and other combinations in this population with few
treatment alternatives.
Keywords
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Article info
Publication history
Published online: April 30, 2022
Accepted:
March 18,
2022
Received in revised form:
March 7,
2022
Received:
January 21,
2022
Identification
Copyright
© 2022 Elsevier Ltd. All rights reserved.
