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
Study Details
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.
Overall Survival
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.
KEY POINTS
- The addition of durvalumab to platinum/etoposide significantly prolonged overall survival vs platinum/etoposide treatment alone—13.0 vs 10.3 months.
- Grade 3 or 4 adverse events occurred in 62% of the durvalumab/platinum/etoposide group vs 62% of the platinum/etoposide group.
Adverse Events
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.
