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
| Autor: | S. Peters, J.-L. Pujol, U. Dafni, M. Dómine, S. Popat, M. Reck, J. Andrade, A. Becker, D. Moro-Sibilot, A. Curioni-Fontecedro, O. Molinier, K. Nackaerts, A. Insa Mollá, R. Gervais, G. López Vivanco, J. Madelaine, J. Mazieres, M. Faehling, F. Griesinger, M. Majem, J.L. González Larriba, M. Provencio Pulla, K. Vervita, H. Roschitzki-Voser, B. Ruepp, P. Mitchell, R.A. Stahel, C. Le Pechoux, D. De Ruysscher, R. Stahel, A. Hiltbrunner, M. Pardo-Contreras, A. Gasca-Ruchti, N. Giacomelli, R. Kammler, N. Marti, R. Pfister, A.C. Piguet, S. Roux, S. Troesch, M. Schneider, R. Schweri, I. Zigomo, Z. Tsourti, P. Zygoura, S. Tsouprou, M. Kassapian, G. Dimopoulou, C. Andriakopoulou, F. Morin, E. Amour, G. Mariaule, N. Archirel, M. Fernandez, E. Pereira, L. Benito, K. Lopez, A. Hernández, S. Chinchen, H. Jurkovic, A. Livingstone, J. Mitchell, M. Walker, S. Ng, C. Steer, K. Briscoe, A. Saqib, E. Abdi, B. Houghton, K. O’Byrne, B.R. Chittajallu, B.G. Hughes, A. Black, H. Werner, G. Zalcman, F. Vaylet, P. Merle, I. Monnet, N. Girard, P.-J. Souquet, F. Barlesi, D. Debieuvre, H. Senellart, M. Poudenx, A. Dixmier, D. Pouessel, J. Cadranel, H. Lena, E. Quoix, S. Friard, C. Audigier-Valette, E. Pichon, K. Kokowski, H. Kirchen, A. Tufman, C. De-Colle, J. de Langen, A. Insa, B. Massutí, M.P. Pulla, S.P. Aix, N. Villanueva, G.L. Vivanco, K. Franks, R. Califano |
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| Přispěvatelé: | RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Radiotherapie, Pulmonary medicine, CCA - Cancer Treatment and quality of life, CCA - Cancer biology and immunology, University of Zurich, Stahel, R A |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Lung Neoplasms 2720 Hematology MULTICENTER 610 Medicine & health Ipilimumab Randomised clinical trial randomised clinical trial 1ST-LINE NIVOLUMAB Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Clinical endpoint small-cell lung cancer Humans RECURRENT ipilimumab Lung cancer nivolumab Limited disease Performance status Small cell lung cancer business.industry Standard treatment Hazard ratio PLUS IPILIMUMAB SCLC Hematology Chemoradiotherapy Middle Aged medicine.disease OPEN-LABEL Nivolumab Oncology 10032 Clinic for Oncology and Hematology limited disease CHECKMATE 032 2730 Oncology Female Prophylactic cranial irradiation business medicine.drug |
| Zdroj: | Annals of oncology : official journal of the European Society for Medical Oncology r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA instname ETOP/IFCT 4-12 STIMULI Collaborators 2022, ' 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 ', Annals of Oncology, vol. 33, no. 1, pp. 67-79 . https://doi.org/10.1016/j.annonc.2021.09.011 Annals of Oncology, 33(1), 67-79. Oxford University Press |
| ISSN: | 1569-8041 0923-7534 |
| DOI: | 10.1016/j.annonc.2021.09.011 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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