Nivolumab ± Ipilimumab in Patients With Pretreated Advanced Neuroendocrine Carcinoma: The GCO-001 NIPINEC Randomized Phase II Trial

Clinical Snapshot

Key Findings

• P Value: Not reported for primary endpoint comparison

• Effect Size: Best ORR: 9.6% vs 20.9%; median PFS ~2 months both arms; median OS ~6 months both arms

• Primary Outcome: Objective response rate at 8 weeks: 7.2% (nivolumab) vs 14.0% (nivolumab-ipilimumab)

• Nnt Or Sensitivity: Number needed to treat approximately 15 patients for one additional response with combination therapy

• Confidence Interval: ORR 95% CI: 2.7-15.1% (nivolumab) vs 7.4-23.1% (combination)

Clinical Application

Both nivolumab and ipilimumab are PBS-listed for other indications; however, cost-effectiveness for NEC would require separate assessment Results applicable to Australian practice; however, limited efficacy may not meet PBS cost-effectiveness thresholds. RACGP guidelines would likely recommend discussion of modest benefits versus toxicity risks Australian patients with advanced neuroendocrine carcinoma who have failed platinum-based chemotherapy and have adequate performance status

Abstract

PURPOSE: There is no standard second-line therapy for gastroenteropancreatic (GEP) and lung large-cell neuroendocrine carcinoma (NEC) after the failure of platinum-based chemotherapy. This study aimed to investigate the efficacy of nivolumab ± ipilimumab. METHODS: The GCO-001-NIPINEC (ClinicalTrials.gov identifier: NCT03591731) trial was a noncomparative, open-label, phase II trial. The main inclusion criteria were age ≥18 years, performance status (PS) ≤2, advanced large- and small-cell GEP-NEC and large-cell lung NEC, and second- or third-line treatment for NECs refractory to platinum-based chemotherapy. Patients were randomly assigned (1:1) and stratified by age and PS to receive nivolumab (3 mg/kg/once every 2 weeks) ± ipilimumab (1 mg/kg/once every 6 weeks) for 2 years or until progression or unacceptable toxicity. The primary end point was objective response rate (ORR) at 8 weeks, assessed by investigators. RESULTS: A total of 185 patients (91 in the nivolumab arm and 94 in the nivolumab-ipilimumab arm) were enrolled between December 2018 and March 2021; 169 were analyzed (median age of 64.5 years, 71% male, 91% PS 0-1). The main primary tumor locations were lungs (50%), colorectal (15%), gastroesophageal (14%), and pancreatic (13%) regions. The ORR at 8 weeks was 7.2% (95% CI, 2.7 to 15.1]) in the nivolumab arm and 14.0% (95% CI, 7.4 to 23.1) in the nivolumab-ipilimumab arm. The best ORR was 9.6% and 20.9%, respectively, whereas the median progression-free and overall survival were approximately 2 months and 6 months in both arms. One treatment-related death occurred, in the nivolumab arm. The grade 3-4 adverse events (≥5%) were asthenia (13%), gamma-glutamyl transferase increase (10%), alkaline phosphatase increase (9%), dyspnea (7%), and anemia (6%) in the nivolumab-ipilimumab arm. CONCLUSION: Nivolumab-ipilimumab could be a second-/third-line treatment option for patients with NECs. However, given the limited magnitude of benefit, studies are warranted to evaluate its use earlier and/or associated with chemotherapy.

References

1. 1.Walter, T. P., Mazieres, J., Otto, J., Lena, H., Lepage, C., Smith, D., Madelaine, J., Gérinière, L., Egenod, T., El Hajbi, F., Ferru, A., Clément-Duchene, C., Madroszyk, A., Brotelle, T., Bouhier-Leporrier, K., Desrame, J., Ghiringhelli, F., Paleiron, N., Khalil, A., Milot, L., Chevallier, O., Couvelard, A., Lantuejoul, S., Langlais, A., Morin, F., Duruisseaux, M., Michel, P., Louvet, C., Westeel, V., & Girard, N. (2026). Nivolumab ± Ipilimumab in Patients With Pretreated Advanced Neuroendocrine Carcinoma: The GCO-001 NIPINEC Randomized Phase II Trial. Journal of Clinical Oncology. https://doi.org/10.1200/JCO-25-01657