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.
Details
Serval ID
serval:BIB_82275164BC57
Type
Article: article from journal or magazin.
Collection
Publications
Institution
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.
Journal
Annals of oncology
Working group(s)
ETOP/IFCT 4-12 STIMULI Collaborators
Contributor(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
Publication state
Published
Issued date
01/2022
Peer-reviewed
Oui
Volume
33
Number
1
Pages
67-79
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
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.
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.
Keywords
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
Create date
04/10/2021 11:38
Last modification date
08/01/2022 7:33
Usage data
