Durvalumab Secures EU Approval for LS-SCLC After CRT

The European Commission has approved durvalumab (Imfinzi) for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following platinum-based chemoradiation therapy (CRT).1

The regulatory decision was supported by data from the phase 3 ADRIATIC trial (NCT03703297), which were presented at the 2024 ASCO Annual Meeting and simultaneously published in the New England Journal of Medicine. Findings showed that patients treated with durvalumab (n = 264) experienced a median overall survival (OS) of 55.9 months (95% CI, 37.3-not evaluable) compared with 33.4 months (95% CI, 25.5-39.9) in patients treated with placebo (n = 266; HR, 0.73; 95% CI, 0.57-0.93; P = .0104).2 The 24- and 36-month OS rates in the durvalumab arm were 68.0% and 56.5%, respectively; these respective rates were 58.5% and 47.6% in the placebo arm.

Furthermore, the median progression-free survival (PFS) was 16.6 months (95% CI, 10.2-28.2) for durvalumab vs 9.2 months (95% CI, 7.4-12.9) for placebo (HR, 0.76; 95% CI, 0.61-0.95; P = .0161). The 18- and 24-month PFS rates were 48.8% and 46.2%, respectively, for durvalumab. These respective rates were 36.1% and 34.2% for placebo.

“This approval marks a turning point for patients with LS-SCLC in Europe, bringing them an immunotherapy option for the first time,” Suresh Senan, PhD, a radiation oncologist at the Amsterdam University Medical Centers in the Netherlands and principal investigator of the ADRIATIC trial, stated in a news release.1 “An unprecedented 57% of patients treated with durvalumab were still alive at 3 years in the ADRIATIC trial. This significant advance establishes a new benchmark in a setting where the standard of care has remained unchanged for decades.”

In December 2024, the FDA approved durvalumab for the treatment of adults with LS-SCLC whose disease has not progressed following concurrent platinum-based CRT.3 This approval was also supported by data from ADRIATIC.

The randomized, double-blind, placebo-controlled, multicenter, international study enrolled patients with stage I to III LS-SCLC (inoperable if stage I or II) whose disease had not progressed following concurrent CRT.2 Patients were required to have a WHO performance status of 0 or 1. Prophylactic cranial irradiation (PCI) was permitted prior to enrollment.

Patients were randomly assigned to receive durvalumab alone at 1500 mg once every 4 weeks; placebo once every 4 weeks; or durvalumab at 1500 mg once every 4 weeks plus tremelimumab-actl (Imjudo) at 75 mg once every 4 weeks for 4 total cycles, followed by durvalumab alone at 1500 mg once every 4 weeks. Treatment continued for a maximum of 24 months or until disease progression or unacceptable toxicity. Notably, data from only the durvalumab monotherapy and placebo arms were presented at the 2024 ASCO Annual Meeting.

Patients were stratified by stage (I/II vs III) and prior PCI (yes vs no).

OS and PFS for durvalumab vs placebo served as the trial’s dual primary end points. OS and PFS for durvalumab plus tremelimumab vs placebo were key secondary end points. Safety was also a secondary end point.

Safety data showed that any-grade adverse effects (AEs) were reported in 94.3% of patients in the durvalumab arm (n = 262) vs 88.3% of patients in the placebo arm (n = 265). The rates of grade 3 or higher AEs were 24.4% and 24.2%, respectively. Serious AEs were reported in 29.8% and 24.2% of patients, respectively. In the durvalumab arm, AEs led to treatment discontinuation and death in 16.4% and 2.7% of patients, respectively. These respective rates were 10.6% and 1.9% in the placebo arm. No treatment-related AEs led to death in the placebo arm compared with 2 patients (0.8%) in the durvalumab arm.

Notably, any-grade pneumonitis or radiation pneumonitis was reported in 38.2% of patients in the durvalumab arm vs 30.2% of patients in the placebo arm. The grade 3/4 rates were 3.1% and 2.6%, respectively. In the experimental arm, pneumonitis led to treatment discontinuation in 8.8% of patients and death in 0.4% of patients. These respective rates were 3.0% and 0% in the control arm.

References

1. Imfinzi approved in the EU as first and only immunotherapy for limited-stage small cell lung cancer. News release. AstraZeneca. March 17, 2025. Accessed March 17, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/imfinzi-approved-in-eu-for-limited-stage-sclc.html
2. Spigel DR, Cheng Y, Cho BC, et al. ADRIATIC: durvalumab (D) as consolidation treatment (tx) for patients (pts) with limited-stage small-cell lung cancer (LS-SCLC). J Clin Oncol. 2024;42(suppl 17):LBA5. doi:10.1200/JCO.2024.42.17_suppl.LBA5
3. FDA approves durvalumab for limited-stage small cell lung cancer. FDA. December 4, 2024. Accessed March 17, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-limited-stage-small-cell-lung-cancer