Trial Analysis Characterizes SCLC Disease Progression

Durvalumab consolidation therapy reduced the rate of extrathoracic metastases vs placebo and prolonged the time to progression or death due to any metastases in patients with limited-stage small-cell lung cancer (LS-SCLC), according to an exploratory analysis of data from the pivotal phase 3 ADRIATIC study.

Extrathoracic metastases occurred in 18.2% and 25.2% of patients in the durvalumab and placebo arms, respectively. The median time to intrathoracic progression or death was 37.3 in the durvalumab arm vs 27.6 months in the placebo arm (hazard ratio [HR], 0.82). The median time to extrathoracic progression or death was not reached in either arm (HR, 0.67), Suresh Senan, MD, PhD, of VU University Medical Center, Amsterdam, the Netherlands, reported at the European Lung Cancer Congress 2025.

The ADRIATIC study included 730 patients with stages I-III LS-SCLC who had not progressed after concurrent chemoradiotherapy. Participants were randomized to receive durvalumab, placebo, or durvalumab plus tremelimumab. The latter arm remained blinded and was not included in the current analysis.

At the first planned interim analysis, durvalumab consolidation was shown to significantly improve the dual primary endpoints of overall survival (OS) and progression-free survival vs placebo, and the current exploratory analysis was performed to characterize patterns of disease progression, Senan explained. 

First instance of progression or death occurred in 52.7% and 63.5% of patients in the durvalumab and placebo arms, respectively. Of those cases, 28.0% vs 29.7% included only intrathoracic progression, 18.2% vs 25.2% included only extrathoracic progression, and 1.5% vs 4.5% included both intra- and extrathoracic progression in the durvalumab vs placebo arm, respectively, he said.

Death in the absence of progression occurred in 4.9% vs 4.1% of patients in the treatment vs placebo arm.

“New extrathoracic lesions at first progression were predominantly in a single organ, particularly the brain,” Senan said. Brain or central nervous system lesions occurred in 6.8% vs 12.4% of patients in the durvalumab vs placebo arms and did not differ based on whether patients received prophylactic cranial radiation.

The median time to brain or CNS progression or death was not reached in either arm (HR, 0.64), he said.

“These data further support the use of consolidation durvalumab as the new standard of care for patients with LS-SCLC who have not progressed after concurrent chemoradiotherapy,” he concluded.

Invited discussant Thierry Berghmans, MD, PhD of the Universite Libre de Bruxellles, Brussels, Belgium, highlighted the decreased incidence of brain metastases with durvalumab vs placebo. He said this appeared to be unrelated to prophylactic cranial radiation and hypothesized that durvalumab may improve OS through better disease control and by preventing the shedding of neoplastic cells into the brain. 

There are limited data regarding the activity of immunotherapy in brain metastases from SCLC, but it is also possible that durvalumab is treating undiagnosed brain metastases, he noted.

The ADRIATIC study was funded by AstraZeneca. Senan disclosed relationships with AstraZeneca, MSD, and ETOP IBCSG Partners Foundation. Berghmans disclosed relationships with InhaTarget, Bayer, Janssen, Merck, Bristol Myers Squibb, Daiichi-Sankyo, Roche, Pfizer, Novartis, Peregrine, Amgen, Novocure, Takeda, and Johnson & Johnson. 

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape Medical News, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.com or on X @SW_MedReporter.