Imfinzi Shows Significant Survival Benefits in Limited-Stage Small-Cell Lung Cancer in Phase III ADRIATIC Trial

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Results from the first planned interim analysis of the Phase III ADRIATIC trial (NCT03703297) show adjuvant treatment with Imfinzi (durvalumab; AstraZeneca) produced significantly longer overall survival (OS) and progression-free survival (PFS) compared to placebo in patients with limited-stage small-cell lung cancer (LS-SCLC).^1,2 These findings, published by The New England Journal of Medicine, are particularly notable as there have not been any advancements in systemic treatments for LS-SCLC over the past three decades, according to the study authors.

“Approximately one third of patients who receive a diagnosis of small-cell lung cancer present with limited-stage disease, for which longest survival is achieved with concurrent thoracic chemoradiotherapy with the use of platinum–etoposide and early thoracic radiotherapy, followed by prophylactic cranial irradiation when indicated,” the study authors wrote. “However, most patients have a disease relapse within 2 years after starting treatment, and overall survival at 5 years ranges from 29% to 34%.”¹

Imfinzi is selective, high-affinity human IgG1 monoclonal antibody that attaches to PD-L1 and blocks interactions with PD-1 and CD80 on activated T cells. Current FDA-approved indications for Imfinzi include for the treatment of unresectable, stage III non-small cell lung cancer (NSCLC) in patients with disease that has not progressed following chemoradiation therapy; for the treatment of ES-SCLC; combined with a limited course of Imjudo (tremelimumab) and chemotherapy to treat metastatic NSCLC; in combination with gemcitabine plus cisplatin to treat locally advanced or metastatic biliary tract cancer; and in combination with Imjudo to treat unresectable hepatocellular carcinoma. Additionally, the drug was approved last month in combination with chemotherapy for adult patients with resectable early-stage (IIA-IIIB) NSCLC without EGFR mutations or ALK rearrangements.³

The ongoing, multicenter, double-blind, randomized, placebo-controlled ADRIATIC trial was comprised of three cohorts—Imfinzi at a dose of 1500 mg, Imfinzi 1500 mg plus Imjudo (tremelimumab) at a dose of 75 mg at four doses only, and placebo—administered every four weeks for up to 24 months. Patients were randomly assigned in a 1:1:1 ratio to the Imfinzi monotherapy cohort (n = 264), the Imfinzi plus Imjudo cohort (n = 200), or the placebo cohort (n = 266).

Imfinzi produced significantly longer OS compared with placebo, at a median of 55.9 months (95% confidence interval [CI], 37.3 to not reached) compared to 33.4 months in the placebo cohort (95% CI, 25.5 to 39.9). Imfinzi also produced significantly longer PFS, at a of median 16.6 months (95% CI, 10.2 to 28.2) compared to 9.2 months (95% CI, 7.4 to 12.9) with placebo.

In terms of safety, adverse events (AEs) at a maximum grade of 3 or 4 were reported among 24.4% of patients administered Imfinzi compared to 24.2% of patients in the placebo cohort. AEs causing discontinuation were observed in 16.4% of patients in the Imfinzi cohort compared to 10.6% in the placebo cohort, and led to death in 2.7% and 1.9% of patients, respectively. Pneumonitis or radiation pneumonitis at a maximum grade of 3 or 4 were reported in 3.1% of patients in the Imfinzi cohort compared to 2.6% of patients in the placebo cohort.¹

“The findings from the ADRIATIC trial are consistent with those of the PACIFIC trial, which involved patients with locally advanced, unresectable NSCLC without disease progression after concurrent chemoradiotherapy and which also showed benefits in overall survival and progression-free survival with adjuvant [Imfinzi] as compared with placebo,” the study authors wrote. “These data suggest a broader mechanism-based effect by which chemoradiotherapy may prime the lung tumor microenvironment for sensitivity to subsequent immunotherapy, as has been described in other tumors. Further studies on the biologic effects of chemoradiotherapy on subsequent immunotherapy, including in different subtypes of small-cell lung cancer, and the investigation of potential biomarkers will be valuable in this context.”¹

References

1. Cheng Y, et al. Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer. Published September 13, 2024. N Engl J Med 2024. https://www.nejm.org/doi/full/10.1056/NEJMoa2404873

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. August 9, 2024. Accessed September 13, 2024. https://clinicaltrials.gov/study/NCT03703297

3. Imfinzi approved in the US for the treatment of resectable non-small cell lung cancer before and after surgery. AstraZeneca. August 16, 2024. Accessed September 13, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/imfinzi-approved-in-us-for-resectable-lung-cancer.html