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

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 phas...

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Autores: 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.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p15913
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=15913
Access Level:acceso abierto
Palabra clave:carboplatin
cisplatin
etoposide
ipilimumab
nivolumab
antineoplastic agent
adult
aged
anemia
anorexia
Article
cancer combination chemotherapy
chemoradiotherapy
clinical feature
cohort analysis
consolidation chemotherapy
constipation
controlled study
coughing
diarrhea
drug effect
drug efficacy
drug safety
drug tolerability
drug withdrawal
dyspnea
fatigue
female
follow up
hazard ratio
human
hyperthyroidism
hypothyroidism
major clinical study
male
monotherapy
multicenter study
multiple cycle treatment
nausea
observational study
overall survival
phase 2 clinical trial
pneumonia
progression free survival
pruritus
radiation dose fractionation
randomized controlled trial
skull irradiation
small cell lung cancer
treatment duration
treatment response
vomiting
adverse event
clinical trial
lung tumor
middle aged
Antineoplastic Combined Chemotherapy Protocols
Chemoradiotherapy
Female
Humans
Ipilimu
Descripción
Sumario: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

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