As reported in The Lancet by Luis Paz-Ares, MD, and colleagues, an interim analysis of the phase III CASPIAN trial has shown an overall survival benefit with the addition of durvalumab to platinum (either cisplatin or carboplatin)/etoposide chemotherapy in the first-line treatment of extensive-stage small cell lung cancer (SCLC).
Luis Paz-Ares, MD
In the open-label trial, patients from 209 sites in 23 countries were randomly assigned 1:1:1 between March 2017 and May 2018 to receive either: durvalumab plus platinum/etoposide (n = 268); durvalumab/tremelimumab/platinum/etoposide (n = 268); or platinum/etoposide alone (n = 269). Patients received up to four cycles of platinum/etoposide plus durvalumab 1,500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1,500 mg every 4 weeks in the durvalumab group, and up to six cycles of platinum-etoposide every 3 weeks plus prophylactic cranial irradiation (at investigator’s discretion) in the platinum/etoposide alone group. Platinum/etoposide consisted of etoposide 80–100 mg/m² on days 1 to 3 of each cycle with investigator’s choice of either carboplatin area under the curve = 5–6, or cisplatin 75–80 mg/m² on day 1 of each cycle.
The primary endpoint was overall survival in the intention-to-treat population. The current interim analysis included only the comparison between the durvalumab/ platinum/etoposide vs platinum/etoposide groups.
At data cutoff, median follow-up was 14.2 months. Median overall survival was 13.0 months in the durvalumab/platinum/etoposide group vs 10.3 months in the platinum/etoposide group (hazard ratio [HR] = 0.73, P = .0047), with 18-month survival rates of 34% vs 25%. Among the 201 patients in each group who received carboplatin, the HR was 0.70 (95% confidence interval [CI] = 0.55–0.89); among the 67 vs 68 patients who received cisplatin, the HR was 0.88 (95% CI = 0.55–1.41).
Progression-free survival could not be formally tested for significance within the trial’s multiple-testing procedure at the time of the overall survival interim analysis. Median progression-free survival at this time was 5.1 months vs 5.4 months (HR = 0.78, 95% CI = 0.65–0.94). Overall, 42% of patients in the durvalumab/platinum/etoposide group and 44% of patients in the platinum/etoposide group received at least one subsequent systemic anticancer therapy after study treatment.
Grade 3 or 4 adverse events occurred in 62% of the durvalumab/platinum/etoposide group vs 62% of the platinum/etoposide group, with the most common in both groups being neutropenia (24% vs 33%) and anemia (9% vs 18%). Serious adverse events occurred in 31% vs 36% of patients. Adverse events led to treatment discontinuation in 9% vs 9% and led to death in 5% vs 6% of patients. Immune-related adverse events occurred in 20% vs 3% of patients, with grade 3 or 4 events occurring in 5% vs < 1%.
The investigators concluded, “First-line durvalumab plus platinum/etoposide significantly improved overall survival in patients with extensive-stage SCLC vs a clinically relevant control group. Safety findings were consistent with the known safety profiles of all drugs received.”
Dr. Paz-Ares, of the Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, is the corresponding author for The Lancet article.
Disclosure: The study was funded by AstraZeneca. For full disclosures of the study authors, visit thelancet.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.