Durvalumab Does Not Meet DFS End Point in Early-Stage NSCLC

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Disease-free survival did not show statistical significance for patients with early-stage non–small cell lung cancer treated with durvalumab.

ADJUVANT BR.31 (NCT02273375) is a prospective, double-blind, placebo-controlled, and randomized trial. A total of 1415 patients were enrolled and randomly assigned 2:1 to receive durvalumab or placebo.

ADJUVANT BR.31 (NCT02273375) is a prospective, double-blind, placebo-controlled, and randomized trial. A total of 1415 patients were enrolled and randomly assigned 2:1 to receive durvalumab or placebo.

Durvalumab (Imfinzi) did not show statistical significance in disease-free survival (DFS), the primary end point, compared with placebo in patients with stage IB to IIIA non–small cell lung cancer (NSCLC) after complete tumor resection with PD-L1 expression of 25% or more, according to a press release on results from the phase 3 ADJUVANT BR.31 trial (NCT02273375).1

In the trial, the safety profile of durvalumab remained consistent with prior reports. Additional results will be presented at an upcoming medical meeting.

The press release noted that durvalumab is the only approved immunotherapy agent with curative intent for patients with unresectable stage III NSCLC who have not progressed after chemoradiotherapy. These results were supported by the phase 3 PACIFIC trial (NCT02125461).

“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 Research and Development at AstraZeneca, said in the press release.1

ADJUVANT BR.31 is a prospective, double-blind, placebo-controlled, and randomized trial.2 A total of 1415 patients were enrolled and randomly assigned 2:1 to receive durvalumab or placebo; triple masking of the patients, care provider, and investigator ensued.

Patients were given durvalumab intravenously at 20 mg/kg every 4 weeks for up to 48 weeks. The placebo arm had matched dosing.

The primary end point was comparing DFS for patients in the aforementioned population without common activating EGFR mutations or ALK rearrangements. Secondary end points included DFS in the subpopulations defined by PD-L1 expression and EGFR/ALK status, overall survival, and lung cancer–specific survival.

Patients were included in the trial if they had a histologically confirmed diagnosis of primary NSCLC based on World Health Organization classification, were classified postoperatively at stage IB, and had complete surgical resection of primary disease. Patients were also included if they had received prior systemic therapy or radiation. Those who had received neoadjuvant platinum-based chemotherapy were not allowed to enroll, and they could not have received prior anticancer therapy for NSCLC. Patients who received radiation were eligible if they had N2 disease and were given postoperative therapy with an ECOG performance status of 0 to 1 and laboratory results within the confines of the criteria.

Patients were not allowed to enroll if they had a history of malignancies except for adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other malignancies curatively treated with no evidence of disease for 5 or more years after treatment. Patients were also excluded if they had a combination of small cell lung cancer and NSCLC plus pulmonary carcinoid tumors or large neuroendocrine tumors, a history of autoimmune disease, a history of primary immunodeficiency, or a live attenuated vaccination given within 30 days of randomization.

Currently, the ADJUVANT BR.31 trial is being conducted around 269 centers in 19 different countries. Countries involved in the study include Canada, the United States, Australia, Europe, and Asia.

In February 2018, the FDA approved durvalumab monotherapy for patients with unresectable stage III NSCLC whose disease had not progressed after concurrent platinum-based chemotherapy and radiation therapy.3 This approval was based on the phase 3 PACIFIC trial.

Currently, durvalumab monotherapy and combination are being evaluated in multiple early-stage lung cancer settings. Trials underway include the PACIFIC-4 study (NCT03833154), PACIFIC-5 study (NCT03706690), PACIFIC-8 study (NCT05211895), and PACIFIC-9 study (NCT05221840).

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://shorturl.at/Gi2iS
  2. Double blind placebo controlled controlled study of adjuvant MEDI4736 in completely resected NSCLC. ClinicalTrials.gov. Accessed June 25, 2024. https://shorturl.at/Qra2P
  3. FDA approves durvalumab after chemoradiation for unresectable stage III NSCLC. News release. FDA. February 16, 2018. Accessed June 25, 2024. https://shorturl.at/aFfQo
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