Four-Year Outcomes of First-Line Nivolumab Plus Ipilimumab for 6 Months Versus Continuation in Patients With Advanced NSCLC: Results of the Randomized IFCT-1701 "DICIPLE" Phase III Trial

Gérard Zalcman; Anne Madroszyk; Edouard Guenzi; Charles Dayen; Olivier Molinier; Thomas Egenod; Nicolas Poté; Didier Debieuvre; Sophie Beaucaire-Danel; Adrien Dixmier; Eric Pichon; Sophie Galland-Girodet; Etienne Giroux-Leprieur; Nicolas Cloarec; Jacques Cadranel; Josiane Otto; Philippe Romand; Laure Favier; Stéphanie Martinez; Céline Mascaux; Luc Odier; Alexis Cortot; Clarisse Audigier-Valette; Alexandra Langlais; Elodie Amour; Franck Morin; Martine Antoine; Valérie Gounant; Virginie Westeel; Anne-Claire Toffart

doi:10.1016/j.jtho.2026.103609

Four-Year Outcomes of First-Line Nivolumab Plus Ipilimumab for 6 Months Versus Continuation in Patients With Advanced NSCLC: Results of the Randomized IFCT-1701 "DICIPLE" Phase III Trial

J Thorac Oncol. 2026 Feb 12:103609. doi: 10.1016/j.jtho.2026.103609. Online ahead of print.

Authors

Gérard Zalcman¹, Anne Madroszyk², Edouard Guenzi³, Charles Dayen⁴, Olivier Molinier⁵, Thomas Egenod⁶, Nicolas Poté³, Didier Debieuvre⁷, Sophie Beaucaire-Danel⁸, Adrien Dixmier⁹, Eric Pichon¹⁰, Sophie Galland-Girodet¹¹, Etienne Giroux-Leprieur¹², Nicolas Cloarec¹³, Jacques Cadranel¹⁴, Josiane Otto¹⁵, Philippe Romand¹⁶, Laure Favier¹⁷, Stéphanie Martinez¹⁸, Céline Mascaux¹⁹, Luc Odier²⁰, Alexis Cortot²¹, Clarisse Audigier-Valette²², Alexandra Langlais²³, Elodie Amour²³, Franck Morin²³, Martine Antoine²⁴, Valérie Gounant²⁵, Virginie Westeel²⁶, Anne-Claire Toffart²⁷

Affiliations

¹ Université Paris Cité, Thoracic Oncology Department & CIC Inserm 1425, Cancer Institute AP-HP.Nord, Hôpital Bichat-Claude Bernard, Paris, France. Electronic address: gerard.zalcman@aphp.fr.
² Centre Régional de lutte contre le Cancer Paoli Calmettes, Marseille, France.
³ Université Paris Cité, Service d'Anatomie Pathologique, Cancer Institute AP-HP.Nord, Hôpital Bichat Claude Bernard, Paris, France.
⁴ Service de Pneumologie et maladies infectieuses, Centre Hospitalier de Saint-Quentin, Saint-Quentin, France.
⁵ Service de Pneumologie et oncologie thoracique, Centre Hospitalier Le Mans, Le Mans, France.
⁶ Service d'Oncologie médicale, CHU Dupuytren, Limoges, France.
⁷ Service de Pneumologie, Hôpital Emile. Muller - GHRMSA, Mulhouse, France.
⁸ Département d'oncologie Médicale, Institut Curie, Paris, France.
⁹ Service de Pneumologie, CHU d'Orléans, Orléans, France.
¹⁰ Service de Pneumologie, CHRU Bretonneau, Tours, France.
¹¹ Service d'oncologue, Polyclinique Bordeaux Nord Aquitaine, Bordeaux, France.
¹² Université Paris Saclay UVSQ, Cancer Institute AP-HP Paris-Saclay, Department of Respiratory Diseases and Thoracic Oncology, Hôpital Ambroise Paré, Boulogne, France.
¹³ Service d'oncologie médicale, Centre Hospitalier d'Avignon, Avignon, France.
¹⁴ Université Paris Sorbonne, Service de Pneumologie et Oncologie thoracique, Cancer Institute Paris-Sorbonne, Hôpital Tenon, AP-HP, Paris, France.
¹⁵ Centre régional de lutte contre le cancer Antoine Lacassagne, Nice, France.
¹⁶ Service de Pneumologie, Centre Hospitalier Alpes Léman, Annemasse, France.
¹⁷ Centre Georges-François Leclerc, Dijon, France.
¹⁸ Service de Pneumologie, Centre Hospitalier Intercommunal Aix-Pertuis, Aix-en-Provence, France.
¹⁹ Service de Pneumologie, Nouvel Hôpital Civil, Strasbourg, France.
²⁰ Service de Peumologie, Centre Hospitalier, Villefranche-sur-Saône, France.
²¹ Service de Pneumologie et d'Oncologie Thoracique, CHU de Lille, France.
²² Service de Pneumologie, CHITS Toulon Sainte Musse, Toulon, France.
²³ Intergroupe Francophone de Cancérologie thoracique (IFCT), Paris, France.
²⁴ Université Paris Sorbonne, Service d'Anatomie Pathologique, Hôpital Tenon, AP-HP, Paris, France.
²⁵ Université Paris Cité, Thoracic Oncology Department & CIC Inserm 1425, Cancer Institute AP-HP.Nord, Hôpital Bichat-Claude Bernard, Paris, France.
²⁶ Université de Franche-Comté, Service de Pneumologie, Oncologie thoracique et allergologie respiratoire, CHU de Jean Minjoz, Besançon, France.
²⁷ Université Grenoble Alpes, Service de Pneumologie et Physiologie, CHU Michallon, La Tronche, France.

PMID: 41690366
DOI: 10.1016/j.jtho.2026.103609

Abstract

Introduction: Optimal first-line immunotherapy duration in metastatic NSCLC with controlled disease remains unclear. We evaluated 6-month nivolumab-ipilimumab (Nivo-Ipi) in patients with disease control (DC).

Methods: This randomized, open-label, noninferiority trial enrolled treatment-naive patients with metastatic NSCLC (aged 18-75 y, Eastern Cooperative Oncology Group performance status 0-1, no actionable genomic alterations). After 6-month induction treatment with Nivo (3 mg/kg biweekly) plus Ipi (1 mg/kg every 6 wk), patients with DC were randomized to continue treatment or stop and resume at disease progression. The primary outcome was progression-free survival (PFS).

Results: Among 265 patients enrolled, 71 were randomized to the continuation control arm (n = 36) or to the experimental arm (n = 35), with trial premature interruption because of the lack of European filing for the immunotherapy combination. Median PFS follow-up was 47.8 months (95% confidence interval [CI]: 43.1-51.0). In the per-protocol population, median PFS was 18.7 months (95% CI: 7.1-37.1) in the continuation arm versus not reached (NR) (95% CI: 16.1-NR) in the experimental arm. Median OS was 55.5 months (95% CI: 32.4-NR) in the continuation arm versus NR in the experimental group. The 18-month OS was 80.6% (95% CI: 63.5-90.2) and 93.8% (95% CI: 77.3-98.4), respectively. Grade 3 to 5 treatment-related adverse event rates were higher in the continuation arm (54.3% versus 23.5%). Median time until definitive quality-of-life deterioration was 15.5 months (95% CI: 10.0-NR) for the continuation arm but NR in the experimental arm (hazard ratio = 0.36, 95% CI: 0.14-0.92, p = 0.03).

Conclusions: Stopping Nivo-Ipi combination at 6 months in DC patients demonstrated no survival harm at 4 years, reduced severe immune-related adverse events, and delayed quality-of-life deterioration.

Keywords: De escalation; Ipilimumab; NSCLC; Nivolumab; Randomized trial.