Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC

By S. Antonia, A. Villegas, D. Daniel, D. Vicente, S. Murakami, R. Hui, T. Kurata, A. Chiappori, K. Lee, M. de Wit and 23 more. New England Journal of Medicine, 2018

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BACKGROUND An earlier analysis in this phase 3 trial showed that durvalumab significantly prolonged progression‐free survival, as compared with placebo, among patients with stage III, unresectable non–small‐cell lung cancer (NSCLC) who did not have disease progression after concurrent chemoradiotherapy. Here we report the results for the second primary end point of overall survival. METHODS We randomly assigned patients, in a 2:1 ratio, to receive durvalumab intravenously, at a dose of 10 mg per kilogram of body weight, or matching placebo every 2 weeks for up to 12 months. Randomization occurred 1 to 42 days after the patients had received chemoradiotherapy and was stratified according to age, sex, and smoking history. The primary end points were progression‐free survival (as assessed by blinded independent central review) and overall survival. Secondary end points included the time to death or distant metastasis, the time to second progression, and safety. RESULTS Of the 713 patients who underwent randomization, 709 received the assigned intervention (473 patients received durvalumab and 236 received placebo). As of March 22, 2018, the median follow‐up was 25.2 months. The 24‐month overall survival rate was 66.3% (95% confidence interval [CI], 61.7 to 70.4) in the durvalumab group, as compared with 55.6% (95% CI, 48.9 to 61.8) in the placebo group (two‐sided P=0.005). Durvalumab significantly prolonged overall survival, as compared with placebo (stratified hazard ratio for death, 0.68; 99.73% CI, 0.47 to 0.997; P=0.0025). Updated analyses regarding progression‐free survival were similar to those previously reported, with a median duration of 17.2 months in the durvalumab group and 5.6 months in the placebo group (stratified hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.63). The median time to death or distant metastasis was 28.3 months in the durvalumab group and 16.2 months in the placebo group (stratified hazard ratio, 0.53; 95% CI, 0.41 to 0.68). A total of 30.5% of the patients in the durvalumab group and 26.1% of those in the placebo group had grade 3 or 4 adverse events of any cause; 15.4% and 9.8% of the patients, respectively, discontinued the trial regimen because of adverse events. CONCLUSIONS Durvalumab therapy resulted in significantly longer overall survival than placebo. No new safety signals were identified. (Funded by AstraZeneca; PACIFIC ClinicalTrials.gov number, NCT02125461.)

Subfields: Oncology, Pulmonary and Respiratory Medicine

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Citations in the corpus

Review of Indications of FDA-Approved Immune Checkpoint Inhibitors per NCCN Guidelines with the Level of Evidence (2020, background): “On 16 February 2108, the FDA approved durvalumab for the treatment of patients with surgically unresectable stage III NSCLC whose cancer has not progressed after treatment with chemoradiation based on a randomized phase III study, the PACIFIC trial, with signficiant improvement in PFS, OS, increased”
Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update (2021, background): “3%, respectively.(265) Studies evaluating ICPi with radiation of varying dosimetric parameters among many cancer types and disease stages are ongoing.”
Immune Checkpoint Inhibitors in Cancer Therapy (2022, background): “In 2018, FDA also approved this drug for patients with unresectable stage III NSCLC that their disease has not progressed after concomitant platinum-based chemotherapy and radiotherapy based on PACIFIC trial results [71].”
Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022, background): “Additionally, the results of the phase 3 study NCT02125461 indicated that sequential durvalumab treatment markedly improved the PFS and OS of NSCLC patients undergoing chemoradiotherapy [84].”
Regulatory mechanisms of PD-1/PD-L1 in cancers (2024, background): “In NSCLC, the ORR of Durvalumab treatment can reach 66.3%, significantly extending the overall survival of patients with phase III and unresectable NSCLC [360].”