CheckMate 451 (NI ; all population), 2019 NCT02538666
nivolumab plus ipilimumab (n=279) vs. placebo (n=275)
randomized controlled trial
nivolumab plus ipilimumab
nivo 1 mg/kg þ ipi 3 mg/kg Q3W intravenously
placebo
3 arms: nivolumab, or nivolumab in combination with ipilimumab, or placebo as maintenance therapy Crossover was not permitted.
Extensive stage SCLC (Es-SCLC) - maintenance (M)
double-blind
168 sites in 32 countries
P3/ two sided and no interim analysis. Overall hierarchical testing procedure will be used to assess thesecondary endpoint (OS/N ; PFS (NI and N))
OS was not significantly prolonged in both arms (nivo plus ipi and nivo versus placebo)
CASPIAN (DT ; all population), 2019 NCT03043872
durvalumab plus tremelimumab plus SoC (n=268) vs. etoposide plus platin (n=269)
randomized controlled trial
durvalumab plus tremelimumab and etoposide plus either cisplatin or carboplatin
durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks,
etoposide plus either cisplatin or carboplatin
etoposide plus either cisplatin or carboplatin In up to six cycles of platinum-etoposide every 3 weeks (etoposide 80-100 mg/m2 on days 1-3 of each cycle with investigator's choice of either carboplatin area under the curve 5-6 mg/mL per min or cisplatin 75-80 mg/m2 (administered on day 1 of each cycle) plus prophylactic cranial irradiation (investigator's discretion).
Crossover from the platinum–etoposide to the immunotherapy plus platinum–etoposide groups was not allowed.
Extensive stage SCLC (Es-SCLC) - 1st Line (L1)
no specific information about EGFR or ALK status at inclusion
open-label
209 sites in 23 countries across Europe, Asia, North America, and South America
P3/ two sided and one interim analysis. A hierarchical multiple testing procedure with an α-exhaustive recycling strategy (OS/D : 4% and OS/DT 1% (recycle OS D)) then hierarchical testing with PFS/D and then PDS/DT
only durvalumab without tremelimumab plus platinum–etoposide significantly improved overall survival in patients with ES-SCLC versus a clinically relevant control group.