ASCO Annual Meeting 2024 unveiled encouraging findings from the ADRIATIC trial, a Phase III study exploring the efficacy of durvalumab as a consolidation treatment for patients with limited-stage small-cell lung cancer (LS-SCLC) who had not progressed following concurrent platinum-based chemoradiotherapy (cCRT).
The ADRIATIC trial is a randomized, double-blind, placebo-controlled study involving 730 patients with Stage I–III LS-SCLC. Eligible patients, with a WHO performance status of 0 or 1, were randomized to receive either durvalumab 1500 mg plus placebo, durvalumab 1500 mg plus tremelimumab 75 mg, or placebo plus placebo every four weeks (Q4W) for four cycles. This was followed by maintenance doses of durvalumab or placebo Q4W until disease progression or intolerable toxicity, for up to 24 months. The study stratified patients by disease stage and whether they received prophylactic cranial irradiation.
The interim analysis, with a data cutoff on January 15, 2024, revealed significant improvements in overall survival (OS) and progression-free survival (PFS) for patients treated with durvalumab compared to placebo. The median OS for the durvalumab group was 55.9 months compared to 33.4 months for the placebo group (HR 0.73; 95% CI 0.57–0.93; p=0.0104). The 24-month OS rate was 68.0% for durvalumab versus 58.5% for placebo, and the 36-month OS rate was 56.5% versus 47.6%. The median PFS was 16.6 months for durvalumab compared to 9.2 months for placebo (HR 0.76; 95% CI 0.61–0.95; p=0.0161). The 18-month PFS rate was 48.8% for durvalumab versus 36.1% for placebo, and the 24-month PFS rate was 46.2% versus 34.2%.
Durvalumab was generally well tolerated. Grade 3/4 adverse events occurred in 24.3% of the durvalumab group versus 24.2% in the placebo group. Discontinuation due to adverse events was slightly higher in the durvalumab arm (16.3% versus 10.6%), and the incidence of pneumonitis/radiation pneumonitis was also higher (38.0% versus 30.2%). Despite these, the safety profile of durvalumab remained consistent with previous studies.
The ADRIATIC trial’s interim results underscore durvalumab’s potential as a new standard of care for patients with LS-SCLC post-cCRT, offering significant survival benefits without introducing new safety concerns. The ongoing analysis of the durvalumab plus tremelimumab arm will further elucidate the role of combination immunotherapy in this setting.
These findings mark a pivotal advancement in the treatment landscape for LS-SCLC, bringing hope for improved patient outcomes.
Reference: Spigel DR et al. ADRIATIC: Durvalumab (D) as consolidation treatment (tx) for patients (pts) with limited-stage small-cell lung cancer (LS-SCLC). Abstract LBA5. American Society of Clinical Oncology 2024.
