Durvalumab as a Potential SoC for Unprogressed LS-SCLC

The standard of care (SoC) for patients (pts) with limited-stage – small cell lung cancer (LS-SCLC) typically involves concurrent platinum-based chemoradiotherapy (cCRT) with or without prophylactic cranial irradiation (PCI).

David R. Spigel and the team aimed to evaluate the efficacy and safety of durvalumab (D) ± tremelimumab (T) as a consolidated therapy for pts with LS-SCLC who had not progressed after cCRT.

This clinical trial involved pts with stage I–III LS-SCLC (inoperable stage I/II) with a WHO performance status of 0/1 who had stable disease post-cCRT. PCI was allowed before randomization. Patients were randomized in 1–42 days post-cCRT to either D 1500 mg + PBO, D 1500 mg + T 75 mg, or PBO + PBO every 4 weeks (Q4W) for 4 cycles. Subsequently, Pts continued on D (for D±T arms) or PBO Q4W until disease progression, intolerable toxicity, or up to 24 months.

The first 600 pts were randomized 1:1:1, with additional pts randomized 1:1 to either D or PBO. Stratification was based on disease stage (I/II vs. III) and PCI receipt (yes vs. no). The dual primary endpoints were overall survival (OS) and progression-free survival (PFS) for D vs PBO, evaluated by blinded independent central review per RECIST v1.1. OS and PFS for D+T vs PBO were alpha-controlled secondary endpoints.

About 730 pts were randomized, with 264 assigned to the D arm and 266 to the PBO arm. Before treatments, Baseline characteristics were balanced between both arms. Radiotherapy sessions for D and PBO arms were once daily for 73.9% and 70.3% of pts, respectively, and it was twice a day for 26.1% and 29.7% of pts, respectively.

PCI was administered to 53.8% of pts in both arms. According to the provisional analysis, as per the data cutoff (January 15, 2024), the median (range) duration of follow-up for OS and PFS in censored pts was 37.2 months (0.1–60.9) and 27.6 months (0.0–55.8), respectively.

Significant Improvement in OS was observed with D relative to PBO with a hazard ratio (HR) of 0.73 (95% CI 0.57–0.93; P=0.0104). The median OS was 5.9 months (95% CI 37.3 – not estimable) and 33.4 months (95% CI 25.5–39.9) in the D and PBO arms respectively. The 24-month OS rate was 68.0% for D vs 58.5% for PBO, and the 36-month OS rate was 56.5% for D vs 47.6% for PBO.

There was a statistically significant elevation in PFS with D vs PBO, with an HR of 0.76 (95% CI 0.61–0.95; P=0.0161). The median PFS was 16.6 months (95% CI 10.2–28.2) for D vs 9.2 months (95% CI 7.4–12.9) for PBO. In month -18, the PFS rate was 48.8% for D compared to 36.1% for PBO, and the 24-month PFS rate was 46.2% for D vs 34.2% for PBO.

The treatment benefit with D was generally consistent across predefined patient subgroups for both OS and PFS. Maximum grade 3/4 all-cause adverse events (AEs) occurred in 24.3% of pts in the D arm vs 24.2% in the PBO arm.

AEs led to treatment discontinuation in 16.3% of pts in the D arm vs 10.6% in the PBO arm and resulted in death in 2.7% vs 1.9%, respectively. Any-grade pneumonitis/radiation pneumonitis was reported in 38.0% of pts in the D arm compared to 30.2% in the PBO arm, with maximum grade 3/4 pneumonitis occurring in 3.0% vs 2.6% of pts, respectively. The D+T arm remains blinded until the next planned analysis.

Researchers observed a significant improvement in OS and PFS after consolidated D therapy post-cCRT relative to PBO in pts with LS-SCLC. D was well tolerated, with minimal side effects and a consistent safety profile.

The trial was sponsored by AstraZeneca.

Source: https://meetings.asco.org/abstracts-presentations/239063

Clinical Trial: https://www.clinicaltrials.gov/study/NCT03703297

Spigel D R, Cheng Y, Cho B C, et al. (2024). “Design and rationale for a phase III, randomized, PBO-controlled trial of D with or without T after concurrent chemoradiotherapy for pts with limited-stage small-cell lung cancer: the ADRIATIC study.” Presented at ASCO 2024. J Clin Oncol 42, 2024 (suppl 17; abstr LBA5), 10.1200/JCO.2024.42.17_suppl.LBA5.