Adjuvant Durvalumab Misses DFS End Point in Resected, PD-L1+ Stage IB-IIIA NSCLC

Adjuvant treatment with durvalumab (Imfinzi) did not lead to a statistically significant improvement in disease-free survival (DFS) compared with placebo after complete tumor resection in patients with stage IB to IIIA non–small cell lung cancer (NSCLC) with PD-L1 expressed on at least 25% of tumor cells, missing the primary end point of the phase 3 ADJUVANT BR.31 trial (NCT02273375).¹

Safety findings for durvalumab were consistent with previous data for the agent, and no new safety signals were reported. AstraZeneca announced that it will present data from ADJUVANT BR.31 at an upcoming medical meeting.

“We are disappointed in the ADJUVANT BR.31 results. [Durvalumab] has helped change the treatment landscape and achieved multiple positive phase 3 trials for patients with earlier stages of lung cancer. We are committed to addressing the remaining unmet need in lung cancer through our broad development program,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, stated in a news release.

ADJUVANT BR.31 was a prospective, double-blind, placebo-controlled, randomized study that enrolled patients at least 18 years of age with histologically confirmed primary non-small cell carcinoma of the lung, per World Health Organization Classification of Tumours. Notably, the trial excluded patients with large-cell neuroendocrine carcinomas.²

Patients were required to have disease post-operatively classified as stage IB, II or IIIA. Notably, patients with T3N2M0 tumors were eligible for the study, despite these tumors being reclassified as stage IIIB under the eighth edition of the International Association for the Study of Lung Cancer staging system. All patients were required to undergo complete surgical resection of the primary tumor with all gross disease removed at the end of surgery and negative surgical margins.

Neoadjuvant chemotherapy was not permitted; however, patients were allowed to receive adjuvant chemotherapy as a part of standard of care. No other prior anticancer therapy was permitted. Patients with N2 disease who only received adjuvant radiation were eligible if they had an ECOG performance status of 0 or 1, as well as adequate neutrophil counts, bilirubin levels, and creatinine clearance.

Key exclusion criteria included a history of other malignancies, except for adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other malignancies curatively treated without evidence of disease for at least 5 years after treatment; the combination of small cell and NSCLC, pulmonary carcinoid tumor, or large-cell neuroendocrine carcinoma; a history of autoimmune disease; a history of primary immunodeficiency; and untreated and/or uncontrolled cardiovascular conditions.

The study was conducted at 269 centers across 19 countries, including Canada, Australia, the United States, and countries in Asia and Europe. Patients were randomly assigned 2:1 to receive intravenous durvalumab at 20 mg/kg or matching placebo once every 4 weeks for up to 48 weeks.1

The primary end point was DFS in patients who did not harbor EGFR mutations or ALK rearrangements and had PD-L1 expressed on at least 25% of tumor cells. Key secondary end points included DFS in patients with PD-L1 expressed on at least 1% of tumor cells and DFS in patients with any PD-L1 status. Overall survival and safety were also secondary end points.

In February 2018, the FDA approved durvalumab for the treatment of patients with unresectable stage III NSCLC whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.³

Other ongoing studies are evaluating durvalumab as monotherapy and in combination therapies in other early-stage NSCLC settings, including in medically inoperable or unresected stage I to II NSCLC in the phase 3 PACIFIC-4 trial (NCT03833154) and in unresectable, stage III NSCLC in the phase 3 PACIFIC-5 (NCT03706690), PACIFIC-8 (NCT05211895) and PACIFIC-9 (NCT05221840) trials.¹

References

1. Update on ADJUVANT BR.31 phase III trial of Imfinzi in non-small cell lung cancer. News release. AstraZeneca. June 25, 2024. Accessed June 25, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/update-on-imfinzi-adjuvant-br31-trial.html
2. Double blind placebo controlled study of adjuvant MEDI4736 in completely resected NSCLC. ClinicalTrials.gov. Updated October 27, 2023. Accessed June 25, 2024. https://www.clinicaltrials.gov/study/NCT02273375
3. FDA approves durvalumab after chemoradiation for unresectable stage III NSCLC. FDA. February 16, 2018. Accessed June 25, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-after-chemoradiation-unresectable-stage-iii-nsclc