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
Por:
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 P., Stahel R.A., Le Pechoux C., De Ruysscher D., Stahel R., Hiltbrunner A., Pardo-Contreras M., Gasca-Ruchti A., Giacomelli N., Kammler R., Marti N., Pfister R., Piguet A.C., Roux S., Troesch S., Schneider M., Schweri R., Zigomo I., Tsourti Z., Zygoura P., Tsouprou S., Kassapian M., Dimopoulou G., Andriakopoulou C., Morin F., Amour E., Mariaule G., Archirel N., Fernandez M., Pereira E., Benito L., Lopez K., Hernández A., Chinchen S., Jurkovic H., Livingstone A., Mitchell J., Walker M., Ng S., Steer C., Briscoe K., Saqib A., Abdi E., Houghton B., O'Byrne K., Chittajallu B.R., Hughes B.G., Black A., Werner H., Zalcman G., Vaylet F., Merle P., Monnet I., Girard N., Souquet P.-J., Barlesi F., Debieuvre D., Senellart H., Poudenx M., Dixmier A., Pouessel D., Cadranel J., Lena H., Quoix E., Friard S., Audigier-Valette C., Pichon E., Kokowski K., Kirchen H., Tufman A., De-Colle C., de Langen J., Insa A., Massutí B., Pulla M.P., Aix S.P., Villanueva N., Vivanco G.L., Franks K., Califano R.
Publicada:
1 ene 2022
Resumen:
Background: 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%. Patients and methods: 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. Results: 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. Conclusions: 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. © 2021 European Society for Medical Oncology
Filiaciones:
Peters S.:
Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
Lausanne University, Lausanne, Switzerland
Pujol J.-L.:
Thoracic Oncology Unit, Hopital Arnaud de Villeneuve, Montpellier, France
Dafni U.:
National and Kapodistrian University of Athens, Athens, Greece
Frontier Science Foundation-Hellas, Athens, Greece
Dómine M.:
Hospital Universitario Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain
Popat S.:
Medicine, Royal Marsden Hospital, London, UK, United Kingdom
Reck M.:
Thoracic Oncology, Lung Clinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany
Andrade J.:
Medical Oncology, Hospital Virgen De La Salud, Toledo, Spain
Becker A.:
Department of Pulmonology, Amsterdam University Medical Center, Amsterdam, Netherlands
Moro-Sibilot D.:
Thoracic Oncology Unit, Centre Hospitalier Universitaire Grenoble-Alpes, Grenoble, France
Curioni-Fontecedro A.:
Department of Medical Oncology and Hematology, University Hospital Zürich, Zürich, Switzerland
Molinier O.:
Department of Respiratory Disease, Centre Hospitalier – Le Mans, Le Mans, France
Nackaerts K.:
Department of Pulmonology, Respiratory Oncology Unit, KU Leuven, Leuven, Belgium
Insa Mollá A.:
Medical Oncology, Hospital Clínico Universitario De Valencia, Valencia, Spain
Gervais R.:
Medical Oncology, Centre François Baclesse, Caen, France
López Vivanco G.:
Medical Oncology, Hospital Universitario Cruces, Barakaldo, Spain
Madelaine J.:
Thoracic Oncology Unit, Centre Hospitalier Universitaire Caen Normandie, Caen, France
Mazieres J.:
Thoracic Oncology, Centre Hospitalier Universitaire Toulouse, Toulouse, France
Faehling M.:
Klinikum Esslingen, Esslingen, Germany
Griesinger F.:
Pius-Hospital Oldenburg, Oldenburg, Germany
Majem M.:
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
González Larriba J.L.:
Hospital Clínico San Carlos, Madrid, Spain
Provencio Pulla M.:
Hospital Puerta de Hierro, Madrid, Spain
Vervita K.:
Frontier Science Foundation-Hellas, Athens, Greece
Roschitzki-Voser H.:
Coordinating Office, European Thoracic Oncology Platform, Bern, Switzerland
Ruepp B.:
Coordinating Office, European Thoracic Oncology Platform, Bern, Switzerland
Mitchell P.:
Olivia Newton-John Cancer Centre, Austin Hospital (VIC), Melbourne, Australia
Stahel R.A.:
Coordinating Office, European Thoracic Oncology Platform, Bern, Switzerland
Le Pechoux C.:
Department of Radiation Oncology, Gustave Roussy, Villejuif, France
De Ruysscher D.:
Maastricht University Medical Center, Department of Radiation Oncology (Maastro), GROW School for Oncology, Maastricht, Netherlands
Stahel R.:
Coordinating Office, European Thoracic Oncology Platform, Bern, Switzerland
Vivanco G.L.:
Medical Oncology, Hospital Universitario Cruces, Barakaldo, Spain
All Open Access, Bronze
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