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Publications

Journal Article Ahead of print 1 citation

PubMed: 41774886 DOI: 10.1200/JCO-25-01657

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

J Clin Oncol

Authors: Thomas Pierre Walter, Julien Mazieres, Josiane Otto, Hervé Lena, Côme Lepage, Denis Smith, Jeannick Madelaine, Laurence Gérinière, Thomas Egenod, Farid El Hajbi, Aurélie Ferru, Christelle Clément-Duchene, Anne Madroszyk, Thibault Brotelle, Karine Bouhier-Leporrier, Jérôme Desrame, François Ghiringhelli, Nicolas Paleiron, Antoine Khalil, Laurent Milot, Olivier Chevallier, Anne Couvelard, Sylvie Lantuejoul, Alexandra Langlais, Franck Morin, Michael Duruisseaux, Pierre Michel, Christophe Louvet, Virginie Westeel, Nicolas Girard

Affiliations

  • Department of Medical Oncology, Hospices Civils de Lyon, Lyon, France; Gastroenterology and technologies for Health, Research Unit INSERM UMR 1052 CNRS UMR 5286, Cancer Research Center of Lyon, Lyon, France.
  • Pulmonology Department, Toulouse University Hospital, Université Paul Sabatier, Toulouse, France.
  • Department of Medical Oncology, Centre Antoine-Lacassagne, Nice, France.
  • Pneumology Department, Centre Hospitalier Universitaire Rennes, Université Rennes 1, INSERM, UMR_S 1242, Centre Eugene Marquis, Rennes, France.
  • Gastroenterology & Digestive Oncology, Dijon University Hospital Le Bocage, Dijon, France.
  • Hepatogastroenterology & Digestive Oncology Bordeaux University Hospital, Bordeaux, France.
  • Department of Pneumology, Caen University Hospital, Caen, France.
  • Respiratory Diseases and Thoracic Oncology Department, Lyon Sud Hospital, Cancer Institute of Hospices Civils de Lyon, Lyon, France.
  • Pneumology Department, Limoges University Hospital, Limoges, France.
  • Oncology Department, Oscar Lambret Centre, Lille, France.
  • Department of Abdominal Oncology, University Hospital of Poitiers, Poitiers, France.
  • Department of Pneumology, Lorraine Cancer Institute, Vandoeuvre-les-Nancy, France.
  • Medical Oncology Department, Paoli-Calmettes Institute, Marseille, France.
  • Medical Oncology Department, Avignon Hospital, Avignon, France.
  • Hepatogastroenterology, Caen University Hospital, Caen, France.
  • Oncology Department, Jean Mermoz Private Hospital, Lyon, France.
  • Medical Oncology Department, Georges-François Leclerc Centre, Dijon, France.
  • Pneumology Department, Saint-Anne Military Teaching Hospital, Toulon, France.
  • Department of Radiology, Neuroradiology Unit, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, Paris, France.
  • Body and VIR Radiology Department, Hospices Civils de Lyon, Hospital Edouard Herriot, Lyon, France.
  • Department of Radiology, Section of Musculoskeletal Imaging and Intervention, LE2I UMR CNRS 6306, François-Mitterrand University Hospital, Dijon, France.
  • Department of Pathology, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, Paris, France.
  • Department of Biopathology, Léon Bérard Centre, Lyon, France.
  • French Cooperative Thoracic Intergroup (IFCT), Paris, France.
  • Pneumology Department, Hospices Civils de Lyon, East Hospital, Lyon, France.
  • Hepatogastroenterology Department, Rouen University Hospital, Rouen, France.
  • Oncology Department, Institut Mutualiste Montsouris, Paris, France.
  • Pneumology Department, Besançon University Hospital, Université Marie et Louis Pasteur, UMR1098 RIGHT, Besançon, France.
  • Institut Curie, Institut Du Thorax Curie-Montsouris, Paris, France; UVSQ, Paris Saclay, Versailles, France.

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.

MeSH

Cells, Lung, Drug Therapy, Nivolumab, Therapeutics, Ipilimumab, Carcinoma, Neuroendocrine, Chemotherapy

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