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.
Détails
ID Serval
serval:BIB_82275164BC57
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
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.
Périodique
Annals of oncology
Collaborateur⸱rice⸱s
ETOP/IFCT 4-12 STIMULI Collaborators
Contributeur⸱rice⸱s
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.
ISSN
1569-8041 (Electronic)
ISSN-L
0923-7534
Statut éditorial
Publié
Date de publication
01/2022
Peer-reviewed
Oui
Volume
33
Numéro
1
Pages
67-79
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.
Mots-clé
Ipilimumab, Limited disease, Nivolumab, Randomised clinical trial, SCLC, Small cell lung cancer, ipilimumab, limited disease, nivolumab, randomised clinical trial, small-cell lung cancer
Pubmed
Web of science
Création de la notice
04/10/2021 10:38
Dernière modification de la notice
08/01/2022 6:33
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