Nivolumab ± Ipilimumab in Patients With Pretreated Advanced Neuroendocrine Carcinoma: The GCO-001 NIPINEC Randomized Phase II Trial
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.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (30)
Thomas Pierre Walter
Medical Oncology Department, Edouard Herriot Hospital, Lyon, France
Julien Mazières
Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, Toulouse, France
Josiane Otto
Department of Medical Oncology, Centre Antoine-Lacassagne, Nice, France
Hervé Lena
Pneumology Department, Centre Hospitalier Universitaire Rennes, Université Rennes 1, INSERM, UMR_S 1242, Centre Eugene Marquis, Rennes, France
Côme Lepage
Gastroenterology & Digestive Oncology, Dijon University Hospital Le Bocage, Dijon, France
Denis Smith
Hepatogastroenterology & Digestive Oncology Bordeaux University Hospital, Bordeaux, France
Jeannick Madelaine
Department of Pneumology, Caen University Hospital, Caen, France
Laurence Gérinière
Respiratory Diseases and Thoracic Oncology Department, Lyon Sud Hospital, Cancer Institute of Hospices Civils de Lyon, Lyon, France
Thomas Egenod
Pneumology Department, Limoges University Hospital, Limoges, France
Farid El Hajbi
Oncology Department, Oscar Lambret Centre, Lille, France
Aurélie Ferru
Department of Abdominal Oncology, University Hospital of Poitiers, Poitiers, France
Christelle Clément-Duchene
Department of Pneumology, Lorraine Cancer Institute, Vandoeuvre-les-Nancy, France
Anne Madroszyk
Medical Oncology Department, Paoli-Calmettes Institute, Marseille, France
Thibault Brotelle
Medical Oncology Department, Avignon Hospital, Avignon, France
Karine Bouhier-Leporrier
Jérôme Desrame
Oncology Department, Jean Mermoz Private Hospital, Lyon, France
François Ghiringhelli
Nicolas Paleiron
Pneumology Department, Saint-Anne Military Teaching Hospital, Toulon, France
Antoine Khalil
Department of Radiology, Neuroradiology Unit, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, Paris, France
Laurent Milot
Body and VIR Radiology Department, Hospices Civils de Lyon, Hospital Edouard Herriot, Lyon, France
Olivier Chevallier
Department of Radiology, Section of Musculoskeletal Imaging and Intervention, LE2I UMR CNRS 6306, François-Mitterrand University Hospital, Dijon, France
Anne Couvelard
Department of Pathology, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, Paris, France
Sylvie Lantuejoul
Department of Biopathology, Léon Bérard Centre, Lyon, France
Alexandra Langlais
Clinical Research Unit, Intergroupe Francophone de Cancérologie Thoracique, Paris, France
Franck Morin
Michaël Duruisseaux
Respiratory Department and Early Phase (EPSILYON), Louis Pradel Hospital, Hospices Civils de Lyon Cancer Institute, Lyon, France
Pierre Michel
Hepatogastroenterology Department, Rouen University Hospital, Rouen, France
Christophe Louvet
Department of Medical Oncology, Institut Mutualiste Montsouris, Paris, France
Virginie Westeel
Pneumology department, CHU Besançon - Hôpital J. MINJOZ, Besançon, France
Nicolas Girard
Institut Curie, Institut du Thorax Curie-Montsouris, Paris