Titre
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.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Peters, S.
Auteure/Auteur
Pujol, J.L.
Auteure/Auteur
Dafni, U.
Auteure/Auteur
Dómine, M.
Auteure/Auteur
Popat, S.
Auteure/Auteur
Reck, M.
Auteure/Auteur
Andrade, J.
Auteure/Auteur
Becker, A.
Auteure/Auteur
Moro-Sibilot, D.
Auteure/Auteur
Curioni-Fontecedro, A.
Auteure/Auteur
Molinier, O.
Auteure/Auteur
Nackaerts, K.
Auteure/Auteur
Insa Mollá, A.
Auteure/Auteur
Gervais, R.
Auteure/Auteur
López Vivanco, G.
Auteure/Auteur
Madelaine, J.
Auteure/Auteur
Mazieres, J.
Auteure/Auteur
Faehling, M.
Auteure/Auteur
Griesinger, F.
Auteure/Auteur
Majem, M.
Auteure/Auteur
González Larriba, J.L.
Auteure/Auteur
Provencio Pulla, M.
Auteure/Auteur
Vervita, K.
Auteure/Auteur
Roschitzki-Voser, H.
Auteure/Auteur
Ruepp, B.
Auteure/Auteur
Mitchell, P.
Auteure/Auteur
Stahel, R.A.
Auteure/Auteur
Le Pechoux, C.
Auteure/Auteur
De Ruysscher, D.
Auteure/Auteur
Contributrices/contributeurs
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.
Vervita, K.
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.
Mitchell, P.
Ng, S.
Steer, C.
Briscoe, K.
Saqib, A.
Abdi, E.
Houghton, B.
O'Byrne, K.
Chittajallu, B.R.
Hughes, B.G.
Black, A.
Nackaerts, K.
Werner, H.
Gervais, R.
Zalcman, G.
Vaylet, F.
Merle, P.
Monnet, I.
Moro-Sibilot, D.
Molinier, O.
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.
Mazieres, J.
Pichon, E.
Faehling, M.
Kokowski, K.
Kirchen, H.
Griesinger, F.
Tufman, A.
De-Colle, C.
de Langen, J.
González Larriba, J.L.
Insa, A.
Majem, M.
Massutí, B.
Pulla, M.P.
Aix, S.P.
Villanueva, N.
Vivanco, G.L.
Andrade, J.
Curioni-Fontecedro, A.
Franks, K.
Califano, R.
Groupes de travail
ETOP/IFCT 4-12 STIMULI Collaborators
Liens vers les personnes
Liens vers les unités
ISSN
1569-8041
Statut éditorial
Publié
Date de publication
2022-01
Volume
33
Numéro
1
Première page
67
Dernière page/numéro d’article
79
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
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.
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.
PID Serval
serval:BIB_82275164BC57
PMID
Date de création
2021-10-04T09:38:23.982Z
Date de création dans IRIS
2025-05-21T00:05:32Z