Consolidation Durvalumab Generates Survival Benefit in LS-SCLC

Consolidation therapy with durvalumab (Imfinzi) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS) compared with placebo in patients with limited stage small cell lung cancer (LS-SCLC) who had not progressed following concurrent chemoradiotherapy (CRT), meeting the dual primary end points of the phase 3 ADRIATIC trial (NCT03703297).¹

Moreover, no new safety signals for durvalumab were observed, and the agent’s safety in the trial was consistent with its known profile.

“Many patients treated for LS-SCLC face disease recurrence and the standard of care has remained unchanged for decades,” Suresh Senan, PhD, professor of Clinical Experimental Radiotherapy at Amsterdam University Medical Center in the Netherlands, and principal investigator of the trial, stated in the press release. “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.”

On March 27, 2020, the FDA approved durvalumab in combination with platinum etoposide and either carboplatin or cisplatin for the first-line treatment of patients with extensive-stage SCLC (ES-SCLC) based on data from the phase 3 CASPIAN trial (NCT03043872).² Durvalumab was also approved for this indication in the European Union, Japan, and China.¹

Moreover, durvalumab remains the global standard of care for patients with unresectable, stage III non–small cell lung cancer (NSCLC) in the curative-intent setting whose disease has not progressed following concurrent CRT. The FDA approved durvalumab for this indication on February 16, 2018, based on data from the phase 3 PACIFIC trial (NCT02125461).³

ADRIATIC was a randomized, double-blind, placebo-controlled, multicenter global trial that enrolled patients 18 years of age or older with histologically or cytologically confirmed, stage I to III LS-SCLC who completed 4 cycles of concurrent CRT within 1 to 42 days prior to randomization and the first study dose, and who did not experience disease progression following definitive concurrent CRT.⁴ Patients were also required to have a life expectancy of 12 weeks or greater at day 1, and an ECOG performance status of 0 or 1 at the time of enrollment.

A total of 730 patients were enrolled onto the trial at 164 medical centers across 19 countries in North and South America, Europe, and Asia.¹ Patients in the first experimental arm were randomly assigned to receive either a fixed 1500 mg dose of intravenous (IV) durvalumab alone, while those in the second experimental arm received durvalumab alongside 75 mg of IV tremelimumab (Imjudo) administered every 4 weeks for up to 4 doses per cycle.⁴ This was followed by treatment with durvalumab every 4 weeks for up to 24 months. In the comparator arm, patients received 2 IV placebo saline solutions every 4 weeks, followed by a single placebo saline solution every 4 weeks for up to 24 months.

The trial’s dual primary end points are PFS and OS for durvalumab monotherapy, with secondary end points of OS and PFS with the combination regimen, safety, and quality of life.

AstraZeneca shared that these results will be presented at a future medical meeting and submitted to global regulatory authorities for review.¹ Evaluation of tremelimumab’s efficacy when added to durvalumab, a key secondary end point in the second experimental arm, remains blinded and will continue to the next planned analysis.

“These exciting results build on the transformative efficacy of Imfinzi 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,” Susan Galbraith, executive vice president, Oncology R&D, at AstraZeneca, added in the same press release.¹ “These data, together with the PACIFIC data in unresectable, stage III NSCLC underscore the pioneering role of [durvalumab] in the treatment of early lung cancer following chemoradiotherapy.”

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://www.astrazeneca.com/media-centre/press-releases/2024/imfinzi-improved-os-and-pfs-in-limited-stage-sclc.html#:~:text=Positive%20high%2Dlevel%20results%20of,limited%2Dstage%20small%20cell%20lung 
2. Imfinzi approved in the US for extensive-stage small cell lung cancer. News Release. AstraZeneca. March 30, 2020. Accessed April 5, 2024. https://www.astrazeneca.com/media-centre/press-releases/2020/imfinzi-approved-in-the-us-for-extensive-stage-small-cell-lung-cancer.html#modal-historic-confirmation
3. FDA approves durvalumab after chemoradiation for unresectable stage III NSCLC. FDA. February 16, 2018. Accessed April 5, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-after-chemoradiation-unresectable-stage-iii-nsclc 
4. 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. Updated January 30, 2024. Accessed April 5, 2024. https://clinicaltrials.gov/study/NCT03703297