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Title: Consolidation nivolumab and ipilimumab versus observation in limited-disease small-cell lung cancer after chemo-radiotherapy - results from the randomised phase II ETOP/IFCT 4-12 STIMULI trial.
Austin Authors: Peters, S ;Pujol, J-L;Dafni, U;Dómine, M;Popat, S;Reck, M;Andrade, J;Becker, A;Moro-Sibilot, D;Curioni-Fontecedro, A;Molinier, O;Nackaerts, K;Insa Mollá, A;Gervais, R;López Vivanco, G;Madelaine, J;Mazieres, J;Faehling, M;Griesinger, F;Majem, M;González Larriba, J L;Provencio Pulla, M;Vervita, K;Roschitzki-Voser, H;Ruepp, B;Mitchell, Paul L R ;Stahel, R A;Le Pechoux, C;De Ruysscher, D
Affiliation: Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland..
Olivia Newton-John Cancer Wellness and Research Centre
Thoracic Oncology Unit, Hopital Arnaud de Villeneuve, Montpellier, France..
National and Kapodistrian University of Athens, Athens, Greece..
Hospital Universitario Fundacion Jimenez Díaz (IIS-FJD), Madrid, Spain..
Medicine, Royal Marsden Hospital, London, UK..
Thoracic Oncology, Lung Clinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany..
Medical Oncology, Hospital Virgen De La Salud, Toledo, Spain..
Department of Pulmonology, Amsterdam University Medical Center, Amsterdam, the Netherlands..
Thoracic Oncology Unit, Centre Hospitalier Universitaire Grenoble-Alpes, Grenoble, France..
Department of Medical Oncology and Hematology, University Hospital Zürich, Zürich, Switzerland..
Department of Respiratory Disease, Centre Hospitalier - Le Mans, Le Mans, France..
Department of Pulmonology, Respiratory Oncology Unit, KU Leuven, Leuven, Belgium..
Medical Oncology, Hospital Clínico Universitario De Valencia, Valencia, Spain..
Medical Oncology, Centre François Baclesse, Caen, France..
Medical Oncology, Hospital Universitario Cruces, Barakaldo, Spain..
Thoracic Oncology, Centre Hospitalier Universitaire Toulouse, Toulouse, France..
Klinikum Esslingen, Esslingen, Germany..
Pius-Hospital Oldenburg, Oldenburg, Germany..
Hospital De La Santa Creu I Sant Pau, Barcelona, Spain..
Hospital Clínico San Carlos, Madrid, Spain..
Hospital Puerta de Hierro, Madrid, Spain..
Frontier Science Foundation-Hellas, Athens, Greece..
Coordinating Office, European Thoracic Oncology Platform, Bern, Switzerland..
Department of Radiation Oncology, Gustave Roussy, Villejuif, France..
Maastricht University Medical Center, Department of Radiation Oncology (Maastro), GROW School for Oncology, Maastricht, Netherlands..
Lausanne University, Lausanne, Switzerland..
Frontier Science Foundation-Hellas, Athens, Greece..
Issue Date: Jan-2022 2021-09-23
Publication information: Annals of oncology : official journal of the European Society for Medical Oncology 2022; 33(1): 67-79
Abstract: Concurrent chemotherapy and thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) is the standard treatment in limited-disease small-cell lung cancer (LD-SCLC), with 5-year overall survival (OS) of only 25% to 33%. STIMULI is a 1:1 randomised phase II trial aiming to demonstrate superiority of consolidation combination immunotherapy versus observation after chemo-radiotherapy plus PCI (protocol amendment-1). Consolidation immunotherapy consisted of four cycles of nivolumab [1 mg/kg, every three weeks (Q3W)] plus ipilimumab (3 mg/kg, Q3W), followed by nivolumab monotherapy (240 mg, Q2W) for up to 12 months. Patient recruitment closed prematurely due to slow accrual and the statistical analyses plan was updated to address progression-free survival (PFS) as the only primary endpoint. Of the 222 patients enrolled, 153 were randomised (78: experimental; 75: observation). Among the randomised patients, median age was 62 years, 60% males, 34%/65% current/former smokers, 31%/66% performance status (PS) 0/1. Up to 25 May 2020 (median follow-up 22.4 months), 40 PFS events were observed in the experimental arm, with median PFS 10.7 months [95% confidence interval (CI) 7.0-not estimable (NE)] versus 42 events and median 14.5 months (8.2-NE) in the observation, hazard ratio (HR) = 1.02 (0.66-1.58), two-sided P = 0.93. With updated follow-up (03 June 2021; median: 35 months), median OS was not reached in the experimental arm, while it was 32.1 months (26.1-NE) in observation, with HR = 0.95 (0.59-1.52), P = 0.82. In the experimental arm, median time-to-treatment-discontinuation was only 1.7 months. CTCAE v4 grade ≥3 adverse events were experienced by 62% of patients in the experimental and 25% in the observation arm, with 4 and 1 fatal, respectively. The STIMULI trial did not meet its primary endpoint of improving PFS with nivolumab-ipilimumab consolidation after chemo-radiotherapy in LD-SCLC. A short period on active treatment related to toxicity and treatment discontinuation likely affected the efficacy results.
DOI: 10.1016/j.annonc.2021.09.011
Journal: Annals of oncology : official journal of the European Society for Medical Oncology
PubMed URL: 34562610
PubMed URL:
Type: Journal Article
Subjects: SCLC
limited disease
randomised clinical trial
small-cell lung cancer
Appears in Collections:Journal articles

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