Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC

PACIFIC Investigators

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252 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2342-2350
Number of pages9
JournalNew England Journal of Medicine
Volume379
Issue number24
DOIs
Publication statusPublished - 2018 Dec 13

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Chemoradiotherapy
Non-Small Cell Lung Carcinoma
Placebos
Survival
Confidence Intervals
Disease-Free Survival
Random Allocation
Disease Progression
Neoplasm Metastasis
Safety
Survival Rate
Smoking
History
Body Weight

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

PACIFIC Investigators. / Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. In: New England Journal of Medicine. 2018 ; Vol. 379, No. 24. pp. 2342-2350.
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title = "Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC",
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.",
author = "{PACIFIC Investigators} and Antonia, {Scott J.} and Augusto Villegas and Davey Daniel and David Vicente and Shuji Murakami and Rina Hui and Takayasu Kurata and Alberto Chiappori and Lee, {Ki H.} and {De Wit}, Maike and Cho, {Byoung C.} and Maryam Bourhaba and Xavier Quantin and Takaaki Tokito and Tarek Mekhail and David Planchard and Kim, {Young Chul} and Karapetis, {Christos S.} and Sandrine Hiret and Gyula Ostoros and Kaoru Kubota and Gray, {Jhanelle E.} and Luis Paz-Ares and {De Castro Carpe{\~n}o}, Javier and Corinne Faivre-Finn and Martin Reck and Johan Vansteenkiste and Spigel, {David R.} and Catherine Wadsworth and Giovanni Melillo and Maria Taboada and Dennis, {Phillip A.} and Mustafa {\"O}zg{\"u}roğlu",
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month = "12",
day = "13",
doi = "10.1056/NEJMoa1809697",
language = "English",
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}

Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. / PACIFIC Investigators.

In: New England Journal of Medicine, Vol. 379, No. 24, 13.12.2018, p. 2342-2350.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC

AU - PACIFIC Investigators

AU - Antonia, Scott J.

AU - Villegas, Augusto

AU - Daniel, Davey

AU - Vicente, David

AU - Murakami, Shuji

AU - Hui, Rina

AU - Kurata, Takayasu

AU - Chiappori, Alberto

AU - Lee, Ki H.

AU - De Wit, Maike

AU - Cho, Byoung C.

AU - Bourhaba, Maryam

AU - Quantin, Xavier

AU - Tokito, Takaaki

AU - Mekhail, Tarek

AU - Planchard, David

AU - Kim, Young Chul

AU - Karapetis, Christos S.

AU - Hiret, Sandrine

AU - Ostoros, Gyula

AU - Kubota, Kaoru

AU - Gray, Jhanelle E.

AU - Paz-Ares, Luis

AU - De Castro Carpeño, Javier

AU - Faivre-Finn, Corinne

AU - Reck, Martin

AU - Vansteenkiste, Johan

AU - Spigel, David R.

AU - Wadsworth, Catherine

AU - Melillo, Giovanni

AU - Taboada, Maria

AU - Dennis, Phillip A.

AU - Özgüroğlu, Mustafa

PY - 2018/12/13

Y1 - 2018/12/13

N2 - 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.

AB - 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.

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U2 - 10.1056/NEJMoa1809697

DO - 10.1056/NEJMoa1809697

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EP - 2350

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

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