Περίληψη:
Background: Concurrent chemotherapy and thoracic radiotherapy followed
by prophylactic cranial irradiation (PCI) is the standard treatment in
limited-disease small-cell lung cancer (ID-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 dosed 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.
Συγγραφείς:
Peters, S.
Pujol, J-L
Dafni, U.
Domine, M.
Popat, S. and
Reck, M.
Andrade, J.
Becker, A.
Moro-Sibilot, D. and
Curioni-Fontecedro, A.
Molinier, O.
Nackaerts, K.
Molla, A.
Insa
Gervais, R.
Lopez Vivanco, G.
Madelaine, J. and
Mazieres, J.
Faehling, M.
Griesinger, F.
Majem, M. and
Gonzalez Larriba, J. L.
Provencio Pulla, M.
Vervita, K. and
Roschitzki-Voser, H.
Ruepp, B.
Mitchell, P.
Stahel, R. A.
and Le Pechoux, C.
De Ruysscher, D.
ETOP IFCT 4-12 STIMULI
Collaborato
