Most patients with small-cell lung cancer (SCLC) have extensive-stage disease at presentation,
and prognosis remains poor. Recently, immunotherapy has demonstrated clinical activity
in extensive-stage SCLC (ES-SCLC). The CASPIAN trial assessed durvalumab, with or
without tremelimumab, in combination with etoposide plus either cisplatin or carboplatin
(platinum-etoposide) in treatment-naive patients with ES-SCLC.This randomised, open-label,
phase 3 trial was done at 209 sites across 23 countries. Eligible patients were adults
with untreated ES-SCLC, with WHO performance status 0 or 1 and measurable disease
as per Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were randomly
assigned (in a 1:1:1 ratio) to durvalumab plus platinum-etoposide; durvalumab plus
tremelimumab plus platinum-etoposide; or platinum-etoposide alone. All drugs were
administered intravenously. Platinum-etoposide consisted of 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). Patients received up to four cycles of platinum-etoposide plus durvalumab
1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab
1500 mg every 4 weeks in the immunotherapy groups and up to six cycles of platinum-etoposide
every 3 weeks plus prophylactic cranial irradiation (investigator's discretion) in
the platinum-etoposide group. The primary endpoint was overall survival in the intention-to-treat
population. We report results for the durvalumab plus platinum-etoposide group versus
the platinum-etoposide group from a planned interim analysis. Safety was assessed
in all patients who received at least one dose of their assigned study treatment.
This study is registered at ClinicalTrials.gov, NCT03043872, and is ongoing.Patients
were enrolled between March 27, 2017, and May 29, 2018. 268 patients were allocated
to the durvalumab plus platinum-etoposide group and 269 to the platinum-etoposide
group. Durvalumab plus platinum-etoposide was associated with a significant improvement
in overall survival, with a hazard ratio of 0·73 (95% CI 0·59-0·91; p=0·0047]); median
overall survival was 13·0 months (95% CI 11·5-14·8) in the durvalumab plus platinum-etoposide
group versus 10·3 months (9·3-11·2) in the platinum-etoposide group, with 34% (26·9-41·0)
versus 25% (18·4-31·6) of patients alive at 18 months. Any-cause adverse events of
grade 3 or 4 occurred in 163 (62%) of 265 treated patients in the durvalumab plus
platinum-etoposide group and 166 (62%) of 266 in the platinum-etoposide group; adverse
events leading to death occurred in 13 (5%) and 15 (6%) patients.First-line durvalumab
plus platinum-etoposide significantly improved overall survival in patients with ES-SCLC
versus a clinically relevant control group. Safety findings were consistent with the
known safety profiles of all drugs received.AstraZeneca.
