Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin: the phase II DUNE trial (GETNE 1601)

Abstract

Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort (C) 1), G1/2 gastrointestinal (C2), G1/2 pancreatic (C3) and G3 gastroenteropancreatic (GEP) (C4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month (m) disease control rate (DCR) for C1-3 and 9-m overall survival (OS) rate for C4. Median follow-up was 16.5 m; 9-m DCR was 25.9%/35.5%/25% for C1, 2, and 3 respectively. The 9-m OS rate for C4 was 36.1%. Benefit in C4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab was safe in NENs and showed modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS.

Progress in immunotherapy for neuroendocrine neoplasm of the digestive system

“…The median OSs were 29.5 mo, 23.8 mo, and 5.9 mo, respectively[ 40 ]. The 9-month DCRs for these cases were 22.8% (95%CI: 16.0-30.8), and 35.5% (95%CI: 20.5-53.0), 25% (95%CI: 12.6-41.7), and 6.1% (95%CI: 1.3-18.1) for C2 to C4, respectively[ 41 ]. Therefore, this study showed that the therapeutic effectiveness of dual ICI therapy in well-differentiated NENs was limited after the failure of standard treatment and had a relatively lower ORR.…”