The addition of durvalumab to chemotherapy improves overall survival compared with platinum-based chemotherapy in patients with extensive-stage SCLC.
CASPIAN is an open-label, phase 3 study of durvalumab (Imfinzi) with or without tremelimumab plus etoposide and either cisplatin or carboplatin (EP) for use as first-line therapy in patients with extensive-stage SCLC.1,2 At the planned interim analysis, the combination of durvalumab and EP demonstrated a statistically significant improvement in overall survival (OS) compared with EP alone (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.59-0.91; P = .0047).2 During the 2020 ASCO Virtual Scientific Program, researchers presented results from a planned updated analysis of OS for durvalumab plus EP compared with EP alone, as well as the first report of results for durvalumab plus tremelimumab plus EP compared with EP alone.1
Treatment-naïve patients with extensive-stage SCLC and World Health Organization performance score of 0 or 1 were randomized to durvalumab 1500 mg plus EP every 3 weeks, durvalumab (1500 mg) plus tremelimumab (75 mg) plus EP every 3 weeks, or EP alone every 3 weeks.1 In the durvalumab-containing arms, patients received 4 cycles of EP plus durvalumab with or without tremelimumab, followed by maintenance durvalumab (1500 mg) every 4 weeks until disease progression. Patients received 1 additional dose of tremelimumab after EP in the durvalumab plus tremelimumab plus EP arm. In the EP arm, patients received up to 6 cycles of EP and prophylactic cranial irradiation (PCI) at the investigator’s discretion. The study had 2 primary end points: OS for durvalumab plus EP compared with EP, and OS for durvalumab plus tremelimumab plus EP compared with EP alone.1
A total of 805 patients were randomized in the CASPIAN study: 268 to durvalumab plus EP, 268 to durvalumab plus tremelimumab plus EP, and 269 to EP alone.1 Their baseline characteristics were generally well-balanced across arms.1 As of January 27, 2020, median follow-up was 25.1 months (82% maturity).1
The combination of durvalumab plus EP continued to demonstrate improvement in OS compared with EP alone, with an HR of 0.75 (95% CI, 0.62-0.91; nominal P = .0032).1 Median OS in these 2 study arms were 12.9 months and 10.5 months, respectively.1 At 2 years, 22% of patients taking durvalumab plus EP were alive compared with 14% of patients taking EP alone.1 Use of tremelimumab with durvalumab plus EP numerically improved OS but the difference did not reach statistical significance per the prespecified statistical plan.1
Secondary end points included progression-free survival (PFS) and overall response rate (ORR), and both were improved with durvalumab plus EP compared with EP alone.1 Confirmed investigator-assessed responses were similar for durvalumab plus tremelimumab plus EP compared with EP alone: 58% versus 58%.1 Median PFS was also similar for durvalumab plus tremelimumab plus EP compared with EP alone: 4.9 months versus 5.4 months.1
In the 3 study arms, incidences of all-cause adverse events (AEs) of grade 3/4 severity were 62% in the durvalumab plus EP arm, 70% in the durvalumab plus tremelimumab plus EP arm, and 63% in the EP-alone arm.1 AEs leading to discontinuation occurred in 10%, 21%, and 9% of patients taking each regimen.1 AEs leading to death occurred in 5%, 10%, and 6% of patients, respectively.1
Researchers concluded that adding durvalumab to EP demonstrates a significant improvement in OS compared with a robust control arm (EP alone). These data support use of durvalumab plus EP as a new standard of care for first-line extended-stage SCLC with the flexibility of platinum choice. No additional benefit was observed when tremelimumab was combined with durvalumab plus EP in these patients. Safety findings in all study arms remained consistent with the known safety profiles of these drugs.1
1. Paz-Ares LG, Dvorkin M, Chen Y, et al. Durvalumab ± tremelimumab + platinum–etoposide in first–line extensive-stage SCLC (ES-SCLC): updated results from the phase 3 CASPIAN study. J Clin Oncol. 2020;38:suppl (abstract 9002).
2. Paz-Ares LG, Dvorkin M, Chen Y, et al; for the CASPIAN Investigators. Durvalumab plus platinum–etoposide versus platinum–etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;94:P1929-P1939.