Durvalumab Significantly Improves Survival in Limited-Stage SCLC

“ADRIATIC is the first global phase 3 immunotherapy trial to deliver significant, clinically meaningful improvement in survival in this setting, marking a breakthrough for patients with this devastating disease," according to Suresh Senan, PhD.

Durvalumab (Imfinzi) elicited a statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS) compared with placebo among those with limited-stage small cell lung cancer (LS-SCLC) demonstrating no progression following concurrent chemoradiotherapy, according to a press release on findings from the phase 3 ADRIATIC trial (NCT03703297).¹

The safety of durvalumab in this trial was comparable with prior reports of the agent, and investigators reported no new safety signals. An additional experimental arm evaluating tremelimumab (Imjudo) in combination with durvalumab as a secondary end point is still blinded; the trial will continue with its assessment of this arm for the next planned analysis.

Developers plan to present these data at a future medical meeting and share their findings with regulatory health authorities across the world.

“Many patients treated for [LS-SCLC may have] disease recurrence, and the standard of care has remained unchanged for decades,” principal investigator Suresh Senan, PhD, a professor of Clinical Experimental Radiotherapy at the Amsterdam University Medical Center in The Netherlands, said in the press release.¹ “ADRIATIC is the first global phase 3 immunotherapy trial to deliver significant, clinically meaningful improvement in survival in this setting, marking a breakthrough for patients with this devastating disease.”

Investigators of the double-blind, placebo-controlled, multicenter phase 3 ADRIATIC trial are assessing durvalumab monotherapy and durvalumab in combination with tremelimumab vs placebo in 730 patients with LS-SCLC who had no disease progression on concurrent chemoradiation. Patients received durvalumab at 1500 mg intravenously plus placebo every 4 weeks for up to 4 cycles followed by durvalumab at 1500 mg every 4 weeks, durvalumab plus tremelimumab at 75 mg intravenously every 4 weeks for up to 4 cycles followed by durvalumab monotherapy, or treatment with placebo only.²

The trial’s primary end points include PFS and OS. Secondary end points include objective response rate, time to death or distant metastasis, health-related quality of life, pharmacokinetics, PD-L1 expression in tumor and/or immune cells relative to efficacy outcomes, and adverse effects.

Patients 18 years and older with histologically or cytologically confirmed LS-SCLC that is stage I to III who have received 4 cycles of chemotherapy concurrent with radiotherapy completed within 1 to 42 days prior to randomization were eligible for enrollment on the trial. Prior radiotherapy must have been administered as 60 to 66 Gy over 6 weeks or as 45 Gy over 3 weeks. Additional eligibility criteria included having no disease progression following concurrent chemoradiotherapy, a life expectancy of at least 12 weeks, and an ECOG performance status of 0 to 1.

Those who had extensive-stage SCLC or active or prior documented autoimmune or inflammatory disorders were unable to enroll on the trial. Patients were also excluded from enrollment if they had uncontrolled intercurrent illness such as interstitial lung disease; active infection requiring management such as tuberculosis, human immunodeficiency virus, and hepatitis B; or received sequential chemotherapy plus radiotherapy.

“These exciting results build on the transformative efficacy of [durvalumab] in [ES-SCLC] and demonstrate the potential to bring a curative-intent immunotherapy treatment to this earlier-stage setting of [SCLC] for the first time. These data, together with the PACIFIC [NCT02125461] data in unresectable, stage III non-small cell lung cancer, underscore the pioneering role of [durvalumab] in the treatment of early lung cancer following chemoradiotherapy,” Susan Galbraith, executive vice president, oncology research & development at AstraZeneca, said in the press release.¹

References

1. Imfinzi significantly improved overall survival and progression-free survival for patients with limited-stage small cell lung cancer in ADRIATIC phase III trial. News release. AstraZeneca. April 5, 2024. Accessed April 5, 2024. https://tinyurl.com/4ffcnvjm
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. Accessed April 5, 2024. https://tinyurl.com/3stjsuk6