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N Engl J Med. 2018 Dec 13;379(24):2342-2350. doi: 10.1056/NEJMoa1809697. Epub 2018 Sep 25.

Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC.

Collaborators (237)

Hui R, Karapetis C, Jasas K, Obyrne K, Houghton B, Hughes B, Lewis C, Links M, Ng S, Parente P, Gauden S, Bourhaba M, Forget F, Vercauter P, Vansteenkiste J, Canon JL, Cheema P, Vincent M, Murray N, Rothenstein J, Zibdawi L, Bradbury P, Butts C, El-Maraghi R, Bebb D, Acevedo Gaete A, Orellana E, Aren Frontera OR, Quantin X, Hiret S, Planchard D, Mazières J, Renault A, Robinet G, Cortot A, Hilgers W, Poudenx M, Barlesi F, El Kouri C, Perol M, Lena H, Sabatini M, de Wit M, Laack E, Schulz C, Brugger W, Faehling M, Reck M, Wolff T, Fischer J, Emde TO, Scholz C, Kalofonos H, Kotsakis A, Syrigos K, Papazisis K, Zarogoulidis K, Ostoros G, Sztancsik Z, Losonczy G, Csanky E, Nechushtan H, Wollner M, Chella A, Bearz A, Chiuri VE, Garassino M, Gianni L, Brighenti M, Ciardiello F, Milella M, Soto Parra H, Murakami S, Yokoi T, Tokito T, Kubota K, Sugawara S, Atagi S, Hirashima T, Imamura F, Iwamoto Y, Kanda S, Masuda N, Minato K, Nakagawa K, Niho S, Saka H, Takahashi T, Fujisaka Y, Sakai H, Takahashi K, Baba T, Harada M, Kasahara K, Maeda T, Maemondo M, Okamoto I, Takeda Y, Kobayashi K, Nogami N, Kiura K, Lee KH, Cho BC, Kim YC, Park K, Cho E, Kim HK, Lee JS, Son C, Kim SW, Shin SW, Flores O, Gomez Rangel J, Hernandez C, Lopez Chuken Y, De Langen J, van den Borne B, Kloover J, van den Heuvel M, van der Leest C, Aerts J, Rodriguez Pantigoso W, Bermudez Alfaro V, Jassem J, Mandziuk S, Kowalski D, Chopra A, Tan EH, Min CT, Stresko M, Demo P, Packan T, Chovanec J, Cohen G, Jacobs C, Rens D, Baz DV, Paz-Ares Rodriguez L, de Castro Carpeño J, Corral Jaime J, Vidal OJ, Taus Garcia A, Cardenal F, Garcia Gomez R, Holgado Martin E, Ponce Aix S, Porta Balanya R, Isla D, Majem M, Marquez Medina D, Alfaro Lizaso J, Blasco Cordellat A, Sanchez Torres JM, Massuti Sureda B, Hsia TC, Chen YM, Lee KY, Lien YC, Yang CH, Reungwetwattana T, Chewaskulyong B, Geater SL, Ozgüroğlu M, Goksel T, Harputluoglu H, Artac M, Paydas S, Altundag O, Sencan O, Hicks J, Faivre-Finn C, Talbot T, Daniel D, Villegas A, Telivala B, Chiappori A, Mekhail T, Hussein M, McLeod M, Slater D, Uyeki J, Waterhouse D, Chen F, Hao Z, Kelly R, Morgensztern D, Page R, Spira A, Awad M, Beck J, Berg A, Choksi J, Dorroh S, Goldman J, Iannotti N, Kubiak K, Rao S, Chaundry A, Dalsania C, Farrel N, Hermann R, Kuzma C, McIntyre K, Mitchell W, Rodriguez E, Sangal A, Smith D, Zu K, Anderson I, Awad M, Behl D, Edenfield W, Ghazal H, Giaccone G, Hagenstad C, Haigentz M, Harper H, Henderson C, Hrinczenko B, Konduri K, Levine M, Martincic D, Pillai R, Salamat M, Shtivelband M, Singh J, Socoteanu M, Spigel D, Zorsky P, Ferrarotto R, Gomez J, Horn L, Kendall S, Lawler W, Anh T, Khoa MT, Luu NK.

Author information

1
From the H. Lee Moffitt Cancer Center and Research Institute, Tampa (S.J.A., A.C., J.E.G.), Cancer Specialists of North Florida, Jacksonville (A.V.), Florida Cancer Specialists, Fleming Island (A.V.), and Florida Hospital Cancer Institute, Orlando (T.M.) - all in Florida; Tennessee Oncology, Chattanooga (D.D.), and Sarah Cannon Research Institute, Nashville (D.D., D.R.S.) - both in Tennessee; Hospital Universitario Virgen Macarena, Seville (D.V.), and Hospital Universitario 12 de Octubre, CiberOnc, Universidad Complutense and Spanish National Cancer Research Center (L.P.-A.), and Hospital Universitario La Paz (J.C.C.), Madrid - all in Spain; Kanagawa Cancer Center, Yokohama (S.M.), Kansai Medical University Hospital, Hirakata (T.K.), Kurume University Hospital, Kurume (T.T.), and Nippon Medical School Hospital, Tokyo (K.K.) - all in Japan; Westmead Hospital and the University of Sydney, Sydney (R.H.), and Flinders University and Flinders Medical Centre, Adelaide, SA (C.S.K.) - all in Australia; Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju (K.H.L.), Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju (Y.-C.K.) - all in South Korea; Vivantes Klinikum Neukoelln, Berlin (M.W.), and the Lung Clinic, Airway Research Center North, German Center for Lung Research, Grosshansdorf (M.R.) - both in Germany; Centre Hospitalier Universitaire de Liège, Liège (M.B.), and University Hospitals KU Leuven, Leuven (J.V.) - both in Belgium; Centre Hospitalier Universitaire de Montpellier and Institut du Cancer de Montpellier Val d'Aurelle, Montpellier (X.Q.), Institut Gustave Roussy, Villejuif (D.P.), and Institut de Cancérologie de l'Ouest-site René Gauducheau, Saint Herblain (S.H.) - all in France; National Koranyi Institute of Pulmonology, Budapest, Hungary (G.O.); the University of Manchester and the Christie NHS Foundation Trust, Manchester (C.F.-F.), AstraZeneca, Alderley Park (C.W.), and AstraZeneca, Cambridge (M.T.) - all in the United Kingdom; AstraZeneca, Gaithersburg, MD (G.M., P.A.D.); and Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Istanbul, Turkey (M.Ö.).

Abstract

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 .).

PMID:
30280658
DOI:
10.1056/NEJMoa1809697
[Indexed for MEDLINE]

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