Limited-stage small cell lung cancer (LS-SCLC), accounting for roughly 30% of all small cell lung cancer cases, remains an aggressive thoracic malignancy. While patients with LS-SCLC often respond well initially to platinum-based chemotherapy combined with thoracic radiotherapy (cCRT), relapse is common, and long-term survival rates remain disappointingly low. Researchers have been focused on strategies to improve outcomes without compromising quality of life, leading to increased investigation of immunotherapy in this setting.
A recent phase 3 trial, ADRIATIC (NCT03703297), evaluated durvalumab (Imfinzi; AstraZeneca), an immune checkpoint inhibitor targeting the programmed death-ligand 1 (PD-L1), as a consolidation treatment following cCRT in patients with LS-SCLC. The trial assessed both survival and patient-reported outcomes (PROs).
ADRIATIC Trial Overview and Endpoints
ADRIATIC is a global, randomized, double-blind, placebo-controlled trial designed to enroll patients with stages 1 through 3 LS-SCLC who had not experienced disease progression after completing platinum-based cCRT. Participants were randomly assigned in a 1:1 ratio to receive durvalumab or a placebo every four weeks for up to 24 months, beginning within one to 42 days of finishing cCRT. A third arm, investigating the combination of durvalumab and tremelimumab (Imjudo; AstraZeneca), remains blinded for the primary analysis.
The primary objectives of the study were overall survival (OS) and progression-free survival (PFS). Secondary objectives included evaluating patient-reported outcomes (PROs), specifically global health status/quality of life (GHS/QoL), various functioning domains, and symptom burden, using validated questionnaires.
Survival and Efficacy Outcomes
The initial planned interim analysis of the ADRIATIC trial demonstrated a significant improvement in both OS and PFS with durvalumab compared to placebo, establishing a new standard of care for LS-SCLC. The median OS in the durvalumab group was approximately 55.9 months, compared to 33.4 months in the placebo group, representing a 27% reduction in the risk of death (HR, 0.73; p = .01). Median PFS was 16.6 months with durvalumab and 9.2 months with placebo (HR, 0.76; p = .02), confirming the statistical significance of both endpoints. These results have been supported by independent analyses and expert reviews, without identifying any new or unexpected safety concerns, further reinforcing the clinical benefit of durvalumab consolidation in LS-SCLC.
Patient-Reported Outcomes: Quality of Life
Beyond improvements in survival, the PRO data from ADRIATIC are particularly valuable, given the extended duration of maintenance immunotherapy. The published PRO results indicate that the addition of durvalumab consolidation did not lead to a decline in GHS/QoL, functioning, or symptom scores at any point during a follow-up period of 24 months, when compared to placebo. Changes from baseline to various domains were limited and generally below clinically significant thresholds in both treatment arms.
Time to deterioration analyses – which measure how long a patient maintains a stable level of symptom control or functional status – were similar between the durvalumab and placebo groups for most outcomes, suggesting that extended immunotherapy did not accelerate the deterioration of quality of life. Notably, patients receiving durvalumab exhibited a longer median time to deterioration for arm/shoulder pain (25.7 vs 9.1 months; HR, 0.70) and reported higher rates of improvement in chest pain, suggesting potential symptomatic benefits in specific areas.
Clinical Context and Implications
The findings from the ADRIATIC trial are noteworthy both for their efficacy and their impact on patient quality of life. Historically, the treatment landscape for LS-SCLC has seen limited advancements beyond the standard chemoradiotherapy regimen. The breakthrough achieved with durvalumab consolidation signals a shift towards integrating immunotherapy earlier in the treatment of SCLC, mirroring the evolving paradigms seen with durvalumab in non-small cell lung cancer and with other immunotherapy combinations in extensive-stage SCLC.
There is growing recognition of the importance of incorporating PROs as endpoints in clinical trials, particularly when interventions involve prolonged therapy. The ADRIATIC trial’s demonstration that durvalumab does not negatively affect quality of life while simultaneously extending survival underscores its value from both clinical and patient-centered perspectives.
Collectively, these data support the adoption of durvalumab consolidation following cCRT as a new standard of care in LS-SCLC, offering patients improved survival with preserved quality of life. As clinical guidelines are updated, PRO evidence, such as that generated by the ADRIATIC trial, will be crucial in facilitating shared decision-making and personalized care planning. On , the Food and Drug Administration (FDA) approved durvalumab (Imfinzi) for the treatment of adults with limited-stage small cell lung cancer whose cancer has not worsened after completing standard chemotherapy and radiation.
REFERENCES
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Novello S, Cheng Y, Spigel D, et al. Patient-Reported Outcomes with Consolidation Durvalumab Versus Placebo Following Concurrent Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer: Results from the Phase 3 ADRIATIC Trial. J Thorac Oncol. Published online January 30, 2026. Doi:10.1016/j.jtho.2026.103564
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Li Y, Fabio. Durvalumab in Limited-Stage Small Cell Lung Cancer: Clinical Triumph and Toward Sustainable Value. JCO Global Oncology. 2025;11(11):e2500638-e2500638. Doi:10.1200/go-25-00638
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Cheng Y, Spigel DR, Cho BC, et al. Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer. N Engl J Med. 2024;391(14):1313-1327. Doi:10.1056/NEJMoa2404873
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Goodman A. Durvalumab Consolidation Therapy Extends Survival in Limited-Stage Small Cell Lung Cancer. The ASCO Post. Published June 25, 2024. Accessed February 10, 2026. https://ascopost.com/issues/june-25-2024/durvalumab-consolidation-therapy-extends-survival-in-limited-stage-small-cell-lung-cancer
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Brown C. ADRIATIC Trial Shows Survival Benefit of Durvalumab in LS-SCLC. Lung Cancers Today. Published March 3, 2025. Accessed February 10, 2026. https://www.lungcancerstoday.com/post/phase-3-adriatic-trial-results-show-survival-benefit-of-durvalumab-in-ls-sclc
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FDA approves durvalumab for limited-stage small cell lung cancer. FDA. Published December 4, 2024. Accessed February 10, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-limited-stage-small-cell-lung-cancer
