Three-Year Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC—Update from PACIFIC

Jhanelle E. Gray; Augusto Villegas; Davey Daniel; David Vicente; Shuji Murakami; Rina Hui; Takayasu Kurata; Alberto Chiappori; Ki Hyeong Lee; Byoung Chul Cho; David Planchard; Luis Paz-Ares; Corinne Faivre-Finn; Johan F. Vansteenkiste; David R. Spigel; Catherine Wadsworth; Maria Taboada; Phillip A. Dennis; Mustafa Özgüroğlu; Scott J. Antonia

doi:10.1016/j.jtho.2019.10.002

Three-Year Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC—Update from PACIFIC

Jhanelle E. Gray, Augusto Villegas, Davey Daniel, David Vicente, Shuji Murakami, Rina Hui, Takayasu Kurata, Alberto Chiappori, Ki Hyeong Lee, Byoung Chul Cho, David Planchard, Luis Paz-Ares, Corinne Faivre-Finn, Johan F. Vansteenkiste, David R. Spigel, Catherine Wadsworth, Maria Taboada, Phillip A. Dennis, Mustafa Özgüroğlu, Scott J. Antonia

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

287 Citations (Scopus)

Abstract

Introduction: In the phase 3 PACIFIC study of patients with unresectable stage III NSCLC without progression after chemoradiotherapy, durvalumab demonstrated significant improvements versus placebo in the primary end points of progression-free survival (hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.42–65, p < 0.0001) and overall survival (OS) (HR = 0.68, 95% CI: 0.53–0.87, p = 0.00251), with manageable safety and no detrimental effect on patient-reported outcomes. Here, we report 3-year OS rates for all patients randomized in the PACIFIC study. Methods: Patients, stratified by age, sex, and smoking history, were randomized (2:1) to receive durvalumab, 10 mg/kg intravenously every 2 weeks, or placebo for up to 12 months. OS was analyzed by using a stratified log-rank test in the intention-to-treat population. Medians and rates at 12, 24, and 36 months were estimated by the Kaplan-Meier method. Results: As of January 31, 2019, 48.2% of patients had died (44.1% and 56.5% in the durvalumab and placebo groups, respectively). The median duration of follow-up was 33.3 months. The updated OS remained consistent with that previously reported (stratified HR = 0.69 [95% CI: 0.55–0.86]); the median OS was not reached with durvalumab but was 29.1 months with placebo. The 12-, 24- and 36-month OS rates with durvalumab and placebo were 83.1% versus 74.6%, 66.3% versus 55.3%, and 57.0% versus 43.5%, respectively. All secondary outcomes examined showed improvements consistent with previous analyses. Conclusions: Updated OS data from PACIFIC, including 3-year survival rates, demonstrate the long-term clinical benefit with durvalumab after chemoradiotherapy and further establish the PACIFIC regimen as the standard of care in this population.

Original language	English
Pages (from-to)	288-293
Number of pages	6
Journal	Journal of Thoracic Oncology
Volume	15
Issue number	2
DOIs	https://doi.org/10.1016/j.jtho.2019.10.002
Publication status	Published - 2020 Feb

Bibliographical note

Funding Information:
Disclosure: Dr. Gray has received research funding, honoraria, and advisory fees from AstraZeneca. Dr. Villegas has received honoraria from AstraZeneca, Gilead, and Seattle Genetics. Dr. Daniel has received institutional research funding from E.R. Squibb and Sons, AstraZeneca, Boehringer Ingelheim, Genentech, Eli Lilly and Company, Novartis Pharmaceuticals, Pfizer, Celgene, and Roche. Dr. Hui has received advisory fees and honoraria from AstraZeneca, Merck Sharp and Dohme, Novartis, Roche, Bristol-Myers Squibb, and Eli Lilly and Company. Dr. Kurata has received research funding and honoraria from AstraZeneca. Dr. Chiappori has received speaker bureau funding from Genentech, Merck, Takeda, Novartis, Boehringer Ingelheim, and Celgene and research funding from Novartis and Bristol-Myers Squibb. Dr. Planchard has received advisory or lecture fees from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, MedImmune, Novartis, Pfizer, prIME Oncology, Peer CME, and Roche; honoraria from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, and Roche; institutional research funding from AstraZeneca, Bristol-Myers Squibb, AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Merck, Novartis, Pfizer, Roche, Medimmune, Sanofi-Aventis, Taiho Pharma, Novocure, and Daiichi Sankyo; and travel, accommodations, or expenses from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Roche, Merck, Novartis, prIME Oncology, and Pfizer. Dr. Paz-Ares is a board member of Genomica and has received honoraria from Roche/Genentech, Eli Lilly and Company, Pfizer, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp and Dohme, AstraZeneca, Merck Serono, Pharmamar, Novartis, Celgene, Sysmex, Amgen, and Incyte, as well as travel, accommodations, or expenses from Roche, AstraZeneca, AstraZeneca Spain, Merck Sharp and Dohme, Bristol-Myers Squibb, Eli Lilly and Company, and Pfizer. Dr. Faivre-Finn has received research funding and travel support from Merck, AstraZeneca, and Elekta and travel support only from Pfizer. Dr. Vansteenkiste has received institutional research funding from Merck Sharp and Dohme; advisory fees from Apotex, AstraZeneca, Boehringer Ingelheim, Merck Sharp and Dohme, Novartis, and Roche; and honoraria from AstraZeneca, Bristol-Myers Squibb, Merck Sharp and Dohme, and Roche. Ms. Taboada and Dr. Dennis are full-time employees of AstraZeneca with stock ownership. Ms. Wadsworth was a full-time employee of AstraZeneca when the work was conducted. The remaining authors declare no conflict of interest.The authors would like to thank the participating patients, their families, and their caregivers, as well as the PACIFIC investigators and the clinical trial personnel at the 235 centers in 26 countries. This study (NCT02125461) was sponsored by AstraZeneca. Medical writing support, which was in accordance with Good Publication Practice guidelines, was provided by Andrew Gannon, MS, MA, and Hashem Dbouk, PhD, of Cirrus Communications (New York, NY), an Ashfield company, and was funded by AstraZeneca.

Funding Information:
The authors would like to thank the participating patients, their families, and their caregivers, as well as the PACIFIC investigators and the clinical trial personnel at the 235 centers in 26 countries. This study ( NCT02125461 ) was sponsored by AstraZeneca . Medical writing support, which was in accordance with Good Publication Practice guidelines, was provided by Andrew Gannon, MS, MA, and Hashem Dbouk, PhD, of Cirrus Communications (New York, NY), an Ashfield company, and was funded by AstraZeneca .

Publisher Copyright:
© 2019 International Association for the Study of Lung Cancer

All Science Journal Classification (ASJC) codes

Oncology
Pulmonary and Respiratory Medicine

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10.1016/j.jtho.2019.10.002

Cite this

Gray, J. E., Villegas, A., Daniel, D., Vicente, D., Murakami, S., Hui, R., Kurata, T., Chiappori, A., Lee, K. H., Cho, B. C., Planchard, D., Paz-Ares, L., Faivre-Finn, C., Vansteenkiste, J. F., Spigel, D. R., Wadsworth, C., Taboada, M., Dennis, P. A., Özgüroğlu, M., & Antonia, S. J. (2020). Three-Year Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC—Update from PACIFIC. Journal of Thoracic Oncology, 15(2), 288-293. https://doi.org/10.1016/j.jtho.2019.10.002

@article{d252e60a30d44e2eba09606c80c4a05d,

title = "Three-Year Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC—Update from PACIFIC",

abstract = "Introduction: In the phase 3 PACIFIC study of patients with unresectable stage III NSCLC without progression after chemoradiotherapy, durvalumab demonstrated significant improvements versus placebo in the primary end points of progression-free survival (hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.42–65, p < 0.0001) and overall survival (OS) (HR = 0.68, 95% CI: 0.53–0.87, p = 0.00251), with manageable safety and no detrimental effect on patient-reported outcomes. Here, we report 3-year OS rates for all patients randomized in the PACIFIC study. Methods: Patients, stratified by age, sex, and smoking history, were randomized (2:1) to receive durvalumab, 10 mg/kg intravenously every 2 weeks, or placebo for up to 12 months. OS was analyzed by using a stratified log-rank test in the intention-to-treat population. Medians and rates at 12, 24, and 36 months were estimated by the Kaplan-Meier method. Results: As of January 31, 2019, 48.2% of patients had died (44.1% and 56.5% in the durvalumab and placebo groups, respectively). The median duration of follow-up was 33.3 months. The updated OS remained consistent with that previously reported (stratified HR = 0.69 [95% CI: 0.55–0.86]); the median OS was not reached with durvalumab but was 29.1 months with placebo. The 12-, 24- and 36-month OS rates with durvalumab and placebo were 83.1% versus 74.6%, 66.3% versus 55.3%, and 57.0% versus 43.5%, respectively. All secondary outcomes examined showed improvements consistent with previous analyses. Conclusions: Updated OS data from PACIFIC, including 3-year survival rates, demonstrate the long-term clinical benefit with durvalumab after chemoradiotherapy and further establish the PACIFIC regimen as the standard of care in this population.",

author = "Gray, {Jhanelle E.} and Augusto Villegas and Davey Daniel and David Vicente and Shuji Murakami and Rina Hui and Takayasu Kurata and Alberto Chiappori and Lee, {Ki Hyeong} and Cho, {Byoung Chul} and David Planchard and Luis Paz-Ares and Corinne Faivre-Finn and Vansteenkiste, {Johan F.} and Spigel, {David R.} and Catherine Wadsworth and Maria Taboada and Dennis, {Phillip A.} and Mustafa {\"O}zg{\"u}roğlu and Antonia, {Scott J.}",

note = "Funding Information: Disclosure: Dr. Gray has received research funding, honoraria, and advisory fees from AstraZeneca. Dr. Villegas has received honoraria from AstraZeneca, Gilead, and Seattle Genetics. Dr. Daniel has received institutional research funding from E.R. Squibb and Sons, AstraZeneca, Boehringer Ingelheim, Genentech, Eli Lilly and Company, Novartis Pharmaceuticals, Pfizer, Celgene, and Roche. Dr. Hui has received advisory fees and honoraria from AstraZeneca, Merck Sharp and Dohme, Novartis, Roche, Bristol-Myers Squibb, and Eli Lilly and Company. Dr. Kurata has received research funding and honoraria from AstraZeneca. Dr. Chiappori has received speaker bureau funding from Genentech, Merck, Takeda, Novartis, Boehringer Ingelheim, and Celgene and research funding from Novartis and Bristol-Myers Squibb. Dr. Planchard has received advisory or lecture fees from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, MedImmune, Novartis, Pfizer, prIME Oncology, Peer CME, and Roche; honoraria from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, and Roche; institutional research funding from AstraZeneca, Bristol-Myers Squibb, AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Merck, Novartis, Pfizer, Roche, Medimmune, Sanofi-Aventis, Taiho Pharma, Novocure, and Daiichi Sankyo; and travel, accommodations, or expenses from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Roche, Merck, Novartis, prIME Oncology, and Pfizer. Dr. Paz-Ares is a board member of Genomica and has received honoraria from Roche/Genentech, Eli Lilly and Company, Pfizer, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp and Dohme, AstraZeneca, Merck Serono, Pharmamar, Novartis, Celgene, Sysmex, Amgen, and Incyte, as well as travel, accommodations, or expenses from Roche, AstraZeneca, AstraZeneca Spain, Merck Sharp and Dohme, Bristol-Myers Squibb, Eli Lilly and Company, and Pfizer. Dr. Faivre-Finn has received research funding and travel support from Merck, AstraZeneca, and Elekta and travel support only from Pfizer. Dr. Vansteenkiste has received institutional research funding from Merck Sharp and Dohme; advisory fees from Apotex, AstraZeneca, Boehringer Ingelheim, Merck Sharp and Dohme, Novartis, and Roche; and honoraria from AstraZeneca, Bristol-Myers Squibb, Merck Sharp and Dohme, and Roche. Ms. Taboada and Dr. Dennis are full-time employees of AstraZeneca with stock ownership. Ms. Wadsworth was a full-time employee of AstraZeneca when the work was conducted. The remaining authors declare no conflict of interest.The authors would like to thank the participating patients, their families, and their caregivers, as well as the PACIFIC investigators and the clinical trial personnel at the 235 centers in 26 countries. This study (NCT02125461) was sponsored by AstraZeneca. Medical writing support, which was in accordance with Good Publication Practice guidelines, was provided by Andrew Gannon, MS, MA, and Hashem Dbouk, PhD, of Cirrus Communications (New York, NY), an Ashfield company, and was funded by AstraZeneca. Funding Information: The authors would like to thank the participating patients, their families, and their caregivers, as well as the PACIFIC investigators and the clinical trial personnel at the 235 centers in 26 countries. This study ( NCT02125461 ) was sponsored by AstraZeneca . Medical writing support, which was in accordance with Good Publication Practice guidelines, was provided by Andrew Gannon, MS, MA, and Hashem Dbouk, PhD, of Cirrus Communications (New York, NY), an Ashfield company, and was funded by AstraZeneca . Publisher Copyright: {\textcopyright} 2019 International Association for the Study of Lung Cancer",

year = "2020",

month = feb,

doi = "10.1016/j.jtho.2019.10.002",

language = "English",

volume = "15",

pages = "288--293",

journal = "Journal of Thoracic Oncology",

issn = "1556-0864",

publisher = "International Association for the Study of Lung Cancer",

number = "2",

}

Gray, JE, Villegas, A, Daniel, D, Vicente, D, Murakami, S, Hui, R, Kurata, T, Chiappori, A, Lee, KH, Cho, BC, Planchard, D, Paz-Ares, L, Faivre-Finn, C, Vansteenkiste, JF, Spigel, DR, Wadsworth, C, Taboada, M, Dennis, PA, Özgüroğlu, M & Antonia, SJ 2020, 'Three-Year Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC—Update from PACIFIC', Journal of Thoracic Oncology, vol. 15, no. 2, pp. 288-293. https://doi.org/10.1016/j.jtho.2019.10.002

TY - JOUR

T1 - Three-Year Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC—Update from PACIFIC

AU - Gray, Jhanelle E.

AU - Villegas, Augusto

AU - Daniel, Davey

AU - Vicente, David

AU - Murakami, Shuji

AU - Hui, Rina

AU - Kurata, Takayasu

AU - Chiappori, Alberto

AU - Lee, Ki Hyeong

AU - Cho, Byoung Chul

AU - Planchard, David

AU - Paz-Ares, Luis

AU - Faivre-Finn, Corinne

AU - Vansteenkiste, Johan F.

AU - Spigel, David R.

AU - Wadsworth, Catherine

AU - Taboada, Maria

AU - Dennis, Phillip A.

AU - Özgüroğlu, Mustafa

AU - Antonia, Scott J.

N1 - Funding Information: Disclosure: Dr. Gray has received research funding, honoraria, and advisory fees from AstraZeneca. Dr. Villegas has received honoraria from AstraZeneca, Gilead, and Seattle Genetics. Dr. Daniel has received institutional research funding from E.R. Squibb and Sons, AstraZeneca, Boehringer Ingelheim, Genentech, Eli Lilly and Company, Novartis Pharmaceuticals, Pfizer, Celgene, and Roche. Dr. Hui has received advisory fees and honoraria from AstraZeneca, Merck Sharp and Dohme, Novartis, Roche, Bristol-Myers Squibb, and Eli Lilly and Company. Dr. Kurata has received research funding and honoraria from AstraZeneca. Dr. Chiappori has received speaker bureau funding from Genentech, Merck, Takeda, Novartis, Boehringer Ingelheim, and Celgene and research funding from Novartis and Bristol-Myers Squibb. Dr. Planchard has received advisory or lecture fees from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, MedImmune, Novartis, Pfizer, prIME Oncology, Peer CME, and Roche; honoraria from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, and Roche; institutional research funding from AstraZeneca, Bristol-Myers Squibb, AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Merck, Novartis, Pfizer, Roche, Medimmune, Sanofi-Aventis, Taiho Pharma, Novocure, and Daiichi Sankyo; and travel, accommodations, or expenses from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Roche, Merck, Novartis, prIME Oncology, and Pfizer. Dr. Paz-Ares is a board member of Genomica and has received honoraria from Roche/Genentech, Eli Lilly and Company, Pfizer, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp and Dohme, AstraZeneca, Merck Serono, Pharmamar, Novartis, Celgene, Sysmex, Amgen, and Incyte, as well as travel, accommodations, or expenses from Roche, AstraZeneca, AstraZeneca Spain, Merck Sharp and Dohme, Bristol-Myers Squibb, Eli Lilly and Company, and Pfizer. Dr. Faivre-Finn has received research funding and travel support from Merck, AstraZeneca, and Elekta and travel support only from Pfizer. Dr. Vansteenkiste has received institutional research funding from Merck Sharp and Dohme; advisory fees from Apotex, AstraZeneca, Boehringer Ingelheim, Merck Sharp and Dohme, Novartis, and Roche; and honoraria from AstraZeneca, Bristol-Myers Squibb, Merck Sharp and Dohme, and Roche. Ms. Taboada and Dr. Dennis are full-time employees of AstraZeneca with stock ownership. Ms. Wadsworth was a full-time employee of AstraZeneca when the work was conducted. The remaining authors declare no conflict of interest.The authors would like to thank the participating patients, their families, and their caregivers, as well as the PACIFIC investigators and the clinical trial personnel at the 235 centers in 26 countries. This study (NCT02125461) was sponsored by AstraZeneca. Medical writing support, which was in accordance with Good Publication Practice guidelines, was provided by Andrew Gannon, MS, MA, and Hashem Dbouk, PhD, of Cirrus Communications (New York, NY), an Ashfield company, and was funded by AstraZeneca. Funding Information: The authors would like to thank the participating patients, their families, and their caregivers, as well as the PACIFIC investigators and the clinical trial personnel at the 235 centers in 26 countries. This study ( NCT02125461 ) was sponsored by AstraZeneca . Medical writing support, which was in accordance with Good Publication Practice guidelines, was provided by Andrew Gannon, MS, MA, and Hashem Dbouk, PhD, of Cirrus Communications (New York, NY), an Ashfield company, and was funded by AstraZeneca . Publisher Copyright: © 2019 International Association for the Study of Lung Cancer

PY - 2020/2

Y1 - 2020/2

N2 - Introduction: In the phase 3 PACIFIC study of patients with unresectable stage III NSCLC without progression after chemoradiotherapy, durvalumab demonstrated significant improvements versus placebo in the primary end points of progression-free survival (hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.42–65, p < 0.0001) and overall survival (OS) (HR = 0.68, 95% CI: 0.53–0.87, p = 0.00251), with manageable safety and no detrimental effect on patient-reported outcomes. Here, we report 3-year OS rates for all patients randomized in the PACIFIC study. Methods: Patients, stratified by age, sex, and smoking history, were randomized (2:1) to receive durvalumab, 10 mg/kg intravenously every 2 weeks, or placebo for up to 12 months. OS was analyzed by using a stratified log-rank test in the intention-to-treat population. Medians and rates at 12, 24, and 36 months were estimated by the Kaplan-Meier method. Results: As of January 31, 2019, 48.2% of patients had died (44.1% and 56.5% in the durvalumab and placebo groups, respectively). The median duration of follow-up was 33.3 months. The updated OS remained consistent with that previously reported (stratified HR = 0.69 [95% CI: 0.55–0.86]); the median OS was not reached with durvalumab but was 29.1 months with placebo. The 12-, 24- and 36-month OS rates with durvalumab and placebo were 83.1% versus 74.6%, 66.3% versus 55.3%, and 57.0% versus 43.5%, respectively. All secondary outcomes examined showed improvements consistent with previous analyses. Conclusions: Updated OS data from PACIFIC, including 3-year survival rates, demonstrate the long-term clinical benefit with durvalumab after chemoradiotherapy and further establish the PACIFIC regimen as the standard of care in this population.

AB - Introduction: In the phase 3 PACIFIC study of patients with unresectable stage III NSCLC without progression after chemoradiotherapy, durvalumab demonstrated significant improvements versus placebo in the primary end points of progression-free survival (hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.42–65, p < 0.0001) and overall survival (OS) (HR = 0.68, 95% CI: 0.53–0.87, p = 0.00251), with manageable safety and no detrimental effect on patient-reported outcomes. Here, we report 3-year OS rates for all patients randomized in the PACIFIC study. Methods: Patients, stratified by age, sex, and smoking history, were randomized (2:1) to receive durvalumab, 10 mg/kg intravenously every 2 weeks, or placebo for up to 12 months. OS was analyzed by using a stratified log-rank test in the intention-to-treat population. Medians and rates at 12, 24, and 36 months were estimated by the Kaplan-Meier method. Results: As of January 31, 2019, 48.2% of patients had died (44.1% and 56.5% in the durvalumab and placebo groups, respectively). The median duration of follow-up was 33.3 months. The updated OS remained consistent with that previously reported (stratified HR = 0.69 [95% CI: 0.55–0.86]); the median OS was not reached with durvalumab but was 29.1 months with placebo. The 12-, 24- and 36-month OS rates with durvalumab and placebo were 83.1% versus 74.6%, 66.3% versus 55.3%, and 57.0% versus 43.5%, respectively. All secondary outcomes examined showed improvements consistent with previous analyses. Conclusions: Updated OS data from PACIFIC, including 3-year survival rates, demonstrate the long-term clinical benefit with durvalumab after chemoradiotherapy and further establish the PACIFIC regimen as the standard of care in this population.

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Three-Year Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC—Update from PACIFIC

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