CHMP Recommends Approval of Durvalumab for Limited-Stage Small Cell Lung Cancer

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the approval of durvalumab (Imfinzi) as monotherapy for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following platinum-based chemoradiation.1

This recommendation was based on findings from the phase 3 ADRIATIC trial (NCT03703297) that demonstrated that durvalumab reduced the risk of death by 27% compared with placebo (HR, 0.73; 95% CI, 0.57-0.93; P = .0104).2 The median overall survival (OS) was 55.9 months (95% CI, 37.3-not evaluable) for durvalumab (n = 264) vs 33.4 months (95% CI, 25.5-39.9) for placebo (n = 266). At 3 years, an estimated 56.5% of patients in the durvalumab arm remained alive compared with 47.6% in the placebo arm.

“With [approximately] 57% of patients still alive at 3 years in the ADRIATIC trial, [durvalumab] has the potential to transform treatment for people with LS-SCLC. If approved, these patients will have access to immunotherapy for the first time, redefining expectations of survival outcomes in this setting,” Susan Galbraith, executive vice president of oncology and hematology at AstraZeneca, stated in a news release.1

Durvalumab also led to a statistically significant improvement in progression-free survival (PFS) vs placebo (HR, 0.76; 95% CI, 0.61-0.95; P = .0161).2 The median 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. The 2-year PFS rates were 46.2% and 34.2%, respectively.

“ADRIATIC was the first phase 3 trial in decades to demonstrate a survival benefit in LS-SCLC, reducing the risk of death by 27% in patients treated with durvalumab vs placebo. Today’s positive recommendation from the CHMP means that our patients in Europe are one step closer to gaining access to this practice-changing treatment regimen,” Suresh Senan, PhD, professor of clinical experimental radiotherapy at the Amsterdam University Medical Centers, and principal investigator of the trial, added in a news release.1

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

ADRIATIC Trial Design

The randomized, global, double-blind, placebo-controlled, multicenter ADRIATIC trial enrolled patients with stage I to III LS-SCLC whose disease had not progressed following concurrent chemoradiotherapy.2 Patients were required to have a WHO performance status of 0 or 1. Notably, prophylactic cranial irradiation (PCI) was permitted prior to randomization.

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

Study participants were randomly assigned in a 1:1:1 ratio to receive durvalumab at 1500 mg every 4 weeks for up to 24 months; durvalumab at 1500 mg plus tremelimumab (Imjudo) at 75 mg every 4 weeks for up to 4 doses, followed by durvalumab maintenance at 1500 mg once every 4 weeks for up to 24 months; or placebo every 4 weeks for up to 24 months.

The dual primary end points of the study were PFS and OS for durvalumab monotherapy vs placebo. Key secondary end points included OS and PFS for durvalumab plus tremelimumab vs placebo; and safety and quality-of-life measures.

Safety Observations

The safety profile of durvalumab was generally manageable and consistent with the known profile of the medicine, with no new safety signals observed.1

Any-grade, all-cause adverse effects (AEs) occurred in 94.3% of patients who received durvalumab (n = 262) vs 88.3% of those given placebo (n = 265).2 AEs were grade 3/4 in severity for 24.4% and 24.2% of patients, respectively. Serious AEs occurred in 29.8% of those given durvalumab vs 24.2% of those given placebo.

Additionally, AEs led to treatment discontinuation for 16.4% and 10.6% of patients, respectively. AEs led to death for 2.7% and 1.9% of patients, respectively. Two patients on the durvalumab arm experienced fatal treatment-related AEs compared with no patients in the placebo arm; these treatment-related deaths were due to encephalopathy and pneumonitis.

References

1. Imfinzi was recommended for approval in the EU by CHMP as first and only immunotherapy for limited-stage small cell lung cancer. News release. AstraZeneca. February 3, 2025. Accessed February 3, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/imfinzi-recommended-for-eu-approval-for-ls-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 December 4, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-limited-stage-small-cell-lung-cancer