LBA41 Nivolumab (nivo) ± ipilimumab (ipi) in pre-treated patients with advanced, refractory pulmonary or gastroenteropancreatic poorly differentiated neuroendocrine tumors (NECs) (GCO-001 NIPINEC)

Abstract

Neuroendocrine Carcinomas (NECs) are a distinct family of poorly differentiated morphology, sharing molecular, clinical and outcome characteristics. No standard-of-care exists after the failure of first-line platinum-based chemotherapy (CT) regimens. Nivo±ipi has been reported to provide survival benefit versus standard CT in metastatic solid cancers. GCO-001 NIPINEC is a multicenter, non-comparative, randomized (1:1) phase 2 trial with a two-step design (early stopping for futility after 50% of accrual). Main inclusion criteria were histologically proven NEC (large- and small-cell for gastroenteropancreatic (GEP) NECs, and large-cell for lung NECs), in 2nd or 3rd line refractory to platinum-based CT, and PS 0-2. Patients received nivo 3 mg/kg q2w ± ipi 1 mg/kg q6w, for 2 years or until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) at 8 weeks assessed by investigators (power of 90%, alpha risk at 5% two-sided). Other endpoints included progression-free survival (PFS), overall survival (OS) and safety. NCT number: NCT03591731. From Dec 2018 to Mar 2021, 185 patients (93 GEP and 92 lung) were enrolled in 50 centers. Median age was 64.4 years (range 26.4–87.1), 71% males, 70% smokers, 91% with ECOG PS 0 or 1, 24% with asymptomatic brain metastases. 170 (92%) patients were evaluable for the primary endpoint. ORR at 8 weeks was 7.2% (95%CI [2.7-15.1]) with nivo and 14.9% (95%CI [8.2-24.2]) with nivo+ipi. Median PFS was 1.8 months (95%CI [1.7-2.0]) with nivo and 1.9 months (95%CI [1.6-2.1]) with nivo+ipi. Median OS was 7.2 months (95%CI [3.7-14.1]) with nivo and 5.8 months (95%CI [3.3-7.6]) with nivo+ipi. 3 patients (3.5%) and 7 patients (8.9%) experienced treatment discontinuation because of toxicity with nivo and nivo+ipi respectively. 2 treatment-related deaths were observed with nivo (meningoencephalitis and pneumonitis). Most frequent grade ≥ 3 AEs were asthenia (7.3%), anaemia (6.3%) and alkaline phosphatase increased (5.8%). Nivo+Ipi only reached the primary endpoint in 2nd/3rd line NECs pts with acceptable toxicity.