Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer - PubMed (original) (raw)

Clinical Trial

. 2017 Nov 16;377(20):1919-1929.

doi: 10.1056/NEJMoa1709937. Epub 2017 Sep 8.

Augusto Villegas 1, Davey Daniel 1, David Vicente 1, Shuji Murakami 1, Rina Hui 1, Takashi Yokoi 1, Alberto Chiappori 1, Ki H Lee 1, Maike de Wit 1, Byoung C Cho 1, Maryam Bourhaba 1, Xavier Quantin 1, Takaaki Tokito 1, Tarek Mekhail 1, David Planchard 1, Young-Chul Kim 1, Christos S Karapetis 1, Sandrine Hiret 1, Gyula Ostoros 1, Kaoru Kubota 1, Jhanelle E Gray 1, Luis Paz-Ares 1, Javier de Castro Carpeño 1, Catherine Wadsworth 1, Giovanni Melillo 1, Haiyi Jiang 1, Yifan Huang 1, Phillip A Dennis 1, Mustafa Özgüroğlu 1; PACIFIC Investigators

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Clinical Trial

Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer

Scott J Antonia et al. N Engl J Med. 2017.

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Abstract

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. (Funded by AstraZeneca; PACIFIC ClinicalTrials.gov number, NCT02125461 .).

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