BACKGROUND: Most patients with locally advanced, unresectable, non–small-cell lung cancer (NSCLC) have disease progression despite definitive chemoradiotherapy (chemotherapy plus concurrent radiation therapy). This phase 3 study compared the anti–programmed death ligand 1 antibody durvalumab as consolidation therapy with placebo in patients with stage III NSCLC who did not have disease progression after two or more cycles of platinum-based chemoradiotherapy. METHODS: We randomly assigned patients, in a 2:1 ratio, to receive durvalumab (at a dose of 10 mg per kilogram of body weight intravenously) or placebo every 2 weeks for up to 12 months. The study drug was administered 1 to 42 days after the patients had received chemoradiotherapy. The coprimary end points were progression-free survival (as assessed by means of blinded independent central review) and overall survival (unplanned for the interim analysis). Secondary end points included 12-month and 18-month progression-free survival rates, the objective response rate, the duration of response, the time to death or distant metastasis, and safety. RESULTS: Of 713 patients who underwent randomization, 709 received consolidation therapy (473 received durvalumab and 236 received placebo). The median progression-free survival from randomization was 16.8 months (95% confidence interval [CI], 13.0 to 18.1) with durvalumab versus 5.6 months (95% CI, 4.6 to 7.8) with placebo (stratified hazard ratio for disease progression or death, 0.52; 95% CI, 0.42 to 0.65; P<0.001); the 12-month progression-free survival rate was 55.9% versus 35.3%, and the 18-month progression-free survival rate was 44.2% versus 27.0%. The response rate was higher with durvalumab than with placebo (28.4% vs. 16.0%; P<0.001), and the median duration of response was longer (72.8% vs. 46.8% of the patients had an ongoing response at 18 months). The median time to death or distant metastasis was longer with durvalumab than with placebo (23.2 months vs. 14.6 months; P<0.001). Grade 3 or 4 adverse events occurred in 29.9% of the patients who received durvalumab and 26.1% of those who received placebo; the most common adverse event of grade 3 or 4 was pneumonia (4.4% and 3.8%, respectively). A total of 15.4% of patients in the durvalumab group and 9.8% of those in the placebo group discontinued the study drug because of adverse events. CONCLUSIONS: Progression-free survival was significantly longer with durvalumab than with placebo. The secondary end points also favored durvalumab, and safety was similar between the groups.
Bibliographical noteFunding Information:
Dr. Antonia reports receiving fees for serving on an advisory board from AstraZeneca; Dr. Villegas, receiving fees for serving on a speakers’ bureau from Celgene, Alexion, and Bristol-Myers Squibb; Dr. Hui, receiving fees for serving on an advisory board and lecture fees from AstraZeneca and Merck Sharp & Dohme, fees for serving on an advisory board from Novartis and Pfizer, and lecture fees from Bristol-Myers Squibb and Boehringer In-gelheim; Dr. Chiappori, receiving fees for serving on a speakers’ bureau from Genentech, Merck, Pfizer, Boehringer Ingelheim, and Celgene, fees for serving on a speakers’ bureau and advisory board from Takeda and Novartis, and fees for serving on an advisory board from Bristol-Myers Squibb; Dr. de Wit, receiving lecture fees from AstraZeneca; Dr. Mekhail, receiving grant support and fees for serving on a speakers’ bureau from AstraZeneca; Dr. Planchard, receiving fees for serving on an advisory board from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, and Novartis; Dr. Kim, receiving grant support from AstraZeneca, Roche, Merck, Bristol-Myers Squibb and Ono Pharmaceutical, and Boehringer Ingelheim; Dr. Karapetis, receiving travel support from AstraZeneca; Dr. Hiret, receiving consulting fees and advisory fees from Roche, Astra-Zeneca, and Boehringer Ingelheim; Dr. Kubota, receiving grant support and honoraria from Daiichi Sankyo, Boehringer Ingel-heim, and Taiho, and honoraria from Eli Lilly, Merck Sharp & Dohme, Bristol-Myers Squibb, Amgen, Ono Pharmaceutical, Novartis, and Chugai Pharmaceutical; Dr. Gray, receiving grant support and advisory fees from AstraZeneca; Dr. Paz-Ares, receiving advisory fees from AstraZeneca, Pfizer, Bristol-Myers Squibb, Merck Sharp & Dohme, Lilly, Roche, Merck Serono, Novartis, and Boehringer Ingelheim; Dr. de Castro Carpeño, receiving fees for serving on an advisory board and lecture fees from AstraZeneca, Boehringer Ingelheim, and Merck Sharp & Dohme, fees for serving on an advisory board, lecture fees, and travel support from Bristol-Myers Squibb and Roche, and fees for serving on an advisory board from Merck; Dr. Melillo, being employed by AstraZeneca; Dr. Jiang, being employed by and holding stock options in AstraZeneca; Dr. Huang, being employed by and owning stock in AstraZeneca; and Dr. Dennis, being employed by and owning stock in AstraZeneca. No other potential conflict of interest relevant to this article was reported.
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