FDA Approves Durvalumab for Limited-Stage Small Cell Lung Cancer

The FDA has approved durvalumab (Imfinzi) for the treatment of adults with limited-stage small cell lung cancer whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.¹

The activity of the agent was evaluated in the phase 3 ADRIATIC trial (NCT03703297) in which treatment with durvalumab led to a statistically significant improvement in overall survival (OS) vs placebo (HR, 0.73; 95% CI, 0.57-0.93; P = .0104). The median OS was 55.9 months (95% CI, 37.3-not reached) in the durvalumab arm compared with 33.4 months (95% CI, 25.5-39.9) in the placebo arm.

Durvalumab also produced a statistically significant improvement in progression-free survival (PFS) compared with placebo (HR, 0.76; 95% CI, 0.61-0.95; P = .0161). The median PFS was 16.6 months (95% CI, 10.2-28.2) and 9.2 months (95% CI, 7.4-12.9) in the durvalumab and placebo arms, respectively.

"For the majority of patients therapy has not been curative. Cure is a primary objective, and we've now shown a very significant improvement in median OS of more than 22.5 months, which could be called a breakthrough for this disease," Suresh Senan, MRCP, FRCR, PhD, a professor of clinical experimental radiotherapy at the Amsterdam University Medical Centers, said in an interview with OncLive®.

ADRIATIC was a randomized, double-blind, placebo-controlled trial that enrolled 730 patients with stage I to III LS-SCLC whose disease had not progressed following concurrent platinum-based chemotherapy and radiation therapy.² Patients were required to have a World Health Organization performance status of 0 or 1, and they could not have progressed after concurrent chemoradiation. Prophylactic cranial irradiation (PCI) was allowed prior to randomization.³

Patients (n = 730) were randomly assigned to one of three arms: single-agent durvalumab at 1500 mg every 4 weeks, placebo every 4 weeks, or durvalumab at 1500 mg every 4 weeks plus tremelimumab (Imjudo) at 75 mg every 4 weeks for 4 doses, followed by durvalumab monotherapy given at 1500 mg every 4 weeks (n = 200). Treatment continued until investigator-determined disease progression, unacceptable toxicity, or up to 24 months. Stratification factors included disease stage (I/II vs III) and whether patients received PCI (yes vs no).

The major efficacy outcome measures were OS and PFS for durvalumab monotherapy and placebo assessed by blinded independent central review.¹

Additional efficacy data showed that at the 3-year landmark analysis, the OS rates were 56.5% with durvalumab and 47.6% with placebo.³ At the 2-year landmark analysis, the PFS rate with durvalumab was 46.2% vs 34.2% with placebo.

Regarding safety, any-grade, all-cause adverse effects (AEs) occurred in 94.3% of evaluable patients who received durvalumab (n = 262) vs 88.3% of those given placebo (n = 265); these effects 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.

AEs led to treatment discontinuation for 16.4% and 10.6% of patients, respectively; they resulted in death for 2.7% and 1.9% of patients, respectively. Specifically, two patients on the durvalumab arm experienced treatment-related AEs that proved fatal; causes of death were encephalopathy and pneumonitis.

"[These findings are] very significant because we've had very little change in the treatment paradigm for the past 30 or so years. We [had] hit a bit of a plateau, with a 5-year survival rate around 30% and more than half of patients developing recurrences in the first two years of treatment. Therefore, the findings of the ADRIATIC trial are very significant indeed," Senan said.

References

1. 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
2. Study of durvalumab + tremelimumab, durvalumab, and placebo in limited stage small-cell lung cancer in patients who have not progressed following concurrent chemoradiation therapy (ADRIATIC). ClinicalTrials.gov. Updated November 6, 2024. Accessed December 4, 2024. https://clinicaltrials.gov/study/NCT03703297
3. 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