Four-Year Survival With Durvalumab After Chemoradiotherapy in Stage III NSCLC—an Update From the PACIFIC Trial

Corinne Faivre-Finn, David Vicente, Takayasu Kurata, David Planchard, Luis Paz-Ares, Johan F. Vansteenkiste, David R. Spigel, Marina C. Garassino, Martin Reck, Suresh Senan, Jarushka Naidoo, Andreas Rimner, Yi Long Wu, Jhanelle E. Gray, Mustafa Özgüroğlu, Ki H. Lee, Byoung C. Cho, Terufumi Kato, Maike de Wit, Michael NewtonLu Wang, Piruntha Thiyagarajah, Scott J. Antonia

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Introduction: In the Phase 3, placebo-controlled PACIFIC trial of patients with unresectable, stage III NSCLC without disease progression after concurrent chemoradiotherapy, consolidative durvalumab was associated with significant improvements in the primary end points of overall survival (OS) (hazard ratio [HR] = 0.68; 95% confidence interval [CI]: 0.53–0.87; p = 0.00251; data cutoff, March 22, 2018) and progression-free survival (PFS) (blinded independent central review; Response Evaluation Criteria in Solid Tumors version 1.1) (HR = 0.52; 95% CI: 0.42–65; p < 0.0001; February 13, 2017) with manageable safety. Here, we report updated analyses of OS and PFS, approximately 4 years after the last patient was randomized. Methods: Patients with WHO performance status of 0 or 1 (and any tumor programmed death-ligand 1 status) were randomized (2:1) to intravenous durvalumab (10 mg/kg) or placebo, administered every 2 weeks (≤12 months), stratified by age, sex, and smoking history. OS and PFS were analyzed using a stratified log-rank test in the intent-to-treat population. Medians and 4-year OS and PFS rates were estimated by the Kaplan–Meier method. Results: Overall, 709 of 713 randomized patients received durvalumab (n/N=473/476) or placebo (n/N=236/237). As of March 20, 2020 (median follow-up = 34.2 months; range: 0.2–64.9), updated OS (HR = 0.71; 95% CI: 0.57–0.88) and PFS (HR = 0.55; 95% CI: 0.44–0.67) remained consistent with the primary analyses. The median OS for durvalumab was reached (47.5 mo; placebo, 29.1 months). Estimated 4-year OS rates were 49.6% versus 36.3% for durvalumab versus placebo, and 4-year PFS rates were 35.3% versus 19.5% respectively. Conclusion: These updated exploratory analyses demonstrate durable PFS and sustained OS benefit with durvalumab after chemoradiotherapy. An estimated 49.6% of patients randomized to durvalumab remain alive at 4 years (placebo, 36.3%), and 35.3% remain alive and progression-free (placebo, 19.5%).

Original languageEnglish
Pages (from-to)860-867
Number of pages8
JournalJournal of Thoracic Oncology
Volume16
Issue number5
DOIs
Publication statusPublished - 2021 May

Bibliographical note

Funding Information:
Disclosure: Dr. Faivre-Finn reports receiving research funding from AstraZeneca , Elekta, and NIHR Manchester Biomedical Research Centre; and travel support from AstraZeneca, and Elekta. Dr. Vicente reports receiving research funding from AstraZeneca , Pfizer , Merck Sharp & Dohme , and Roche; and honoraria from AstraZeneca, Pfizer, Bristol-Myers Squibb, Merck Sharp & Dohme, and Roche. Dr. Kurata reports receiving research funding from AstraZeneca , Merck Sharp & Dohme , Bristol-Myers Squibb, Novartis, Takeda, and Chugai; and honoraria from AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Ono, Boehringer Ingelheim, Bristol-Myers Squibb, and Chugai. Dr. Planchard reports receiving consulting, advisory, and/or speakers’ bureau fees from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche, and Samsung. Dr. Paz-Ares reports receiving consulting, advisory, and/or speakers’ bureau fees from Merck Sharp & Dohme, Bristol-Myers Squibb, Roche, AstraZeneca, Eli Lilly, Merck, Novartis, Amgen, Incyte, Takeda, PharmaMar, Ipsen, Blueprint, and Bayer; and has board membership for Altum Sequencing and Genomica. Dr. Vansteenkiste reports receiving research funding from Merck Sharp & Dohme; and consulting, advisory, and/or speakers’ bureau fees from AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, Roche, Pfizer, and Bristol-Myers Squibb. Dr. Spigel reports receiving research funding from AstraZeneca, Genentech/Roche, Novartis, Celgene, Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, AbbVie, Foundation Medicine, GlaxoSmithKline, Eli Lilly, Merck, Nektar, Takeda, Amgen, University of Texas Southwestern Medical Center–Simmons Cancer Center, G1 Therapeutics, Neon Therapeutics, Celldex, Clovis Oncology, Daiichi Sankyo, EMD Serono, Astellas Pharma, GRAIL, Transgene, Aeglea Therapeutics, Tesaro, Ipsen, Janssen, BIND Therapeutics, Eisai, and ImClone Systems; and consulting, advisory, and/or speakers’ bureau fees from AstraZeneca , Genentech/Roche, Novartis, Celgene, Bristol-Myers Squibb, Pfizer , Boehringer Ingelheim, AbbVie, Foundation Medicine, GlaxoSmithKline, Eli Lilly, Merck, Moderna, Nektar, Takeda, Amgen, TRM Oncology, Precision Oncology, Evelo Therapeutics, Illumina, Pharmamar, EMD Serono, Aptitude Health, Dracen Pharmaceuticals, Iksuda Therapeutics, Molecular Templates, Seattle Genetics, TRIPTYCH Health Partners, and Intellisphere. Dr. Garassino reports receiving research funding from Bristol-Myers Squibb, Merck Sharp & Dohme , Roche/Genentech, AstraZeneca, Pfizer, GlaxoSmithKline, Novartis Merck, Incyte, Takeda, Spectrum Pharmaceuticals, and Blueprint Medicines; consulting, advisory, and/or speakers’ bureau fees from Bristol-Myers Squibb, Merck Sharp & Dohme, AstraZeneca, Novartis, Takeda, Roche, Tiziana Life Sciences, Sanofi, Celgene, Daiichi Sankyo, Inivata, Incyte, Pfizer, Seattle Genetics, Eli Lilly and Otsuka; travel, accommodation, and expenses from Pfizer, Roche, and AstraZeneca; and honoraria from Merck Sharp & Dohme, AstraZeneca, GlaxoSmithKline, Takeda, Roche, Bristol-Myers Squibb. Dr. Reck reports receiving consulting, advisory, and/or speakers’ bureau fees from Amgen, AstraZeneca , Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Merck Sharp & Dohme , Novartis, Pfizer , Roche, and Samsung. Dr. Senan reports receiving research funding from AstraZeneca, Varian Medical Systems, and ViewRay, Inc.; consultancy, advisory, and/or speakers’ bureau fees from AstraZeneca, Celgene, Merck Sharp & Dohme, Eli Lilly, and Varian Medical Systems. Dr. Naidoo reports receiving research funding from AstraZeneca, Merck, and Roche/Genentech; consulting, advisory, and/or speakers’ bureau fees from Bristol-Myers Squibb, AstraZeneca, and Roche/Genentech; travel, accommodations, and expenses from Bristol-Myers Squibb and AstraZeneca. Dr. Rimner reports receiving research funding from AstraZeneca , Varian Medical Systems, Merck, Boehringer Ingelheim, and Pfizer; travel, accommodations, and expenses from AstraZeneca , Merck, Research to Practice, Cybrexa, and More Health; and other fees from Elekta. Dr. Wu reports receiving research funding from AstraZeneca, Bristol-Myers Squibb, and Pfizer; and consulting, advisory, and/or speakers’ bureau fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Pfizer, and Sanofi. Dr. Gray reports receiving research funding from Genentech, Merck, Bristol-Myers Squibb, Regeneron, Eli Lilly, Merck KGA, Novartis and Boehringer Ingelheim; and consulting, advisory, and/or speakers’ bureau fees from AstraZeneca, Takeda, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck KGA, Novartis, and Merck. Dr. Lee reports receiving consulting, advisory, and/or speakers’ bureau fees from Bristol-Myers Squibb, Merck Sharp & Dohme, AstraZeneca, and Pfizer. Dr. Cho reports receiving research funding from Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, and Merck Sharp & Dohme; consulting, advisory, and/or speakers’ bureau fees from Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda and Merck Sharp & Dohme; and stock ownership in TheraCanVac, Inc. Dr. Kato reports receiving research funding from AstraZeneca, AbbVie, Amgen, Bristol-Myers Squibb, Chugai, Eli Lilly, Merck, Merck Sharp & Dohme, Novartis, Ono, Pfizer, Taiho, Astellas, Kyorin, Kyowa-Kirin and Regeneron; and consulting, advisory, and/or speakers’ bureau fees from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Chugai, Eli Lilly, Merck, Merck Sharp & Dohme , Novartis, Ono, Pfizer, Taiho, Boehringer Ingelheim, Daiichi Sankyo, F. Hoffman-La Roche, Nippon Kayaku, Nitto Denko, Shionogi, Sumitomo Dainippon, and Takeda. Dr. de Wit reports receiving consulting, advisory, and/or speakers’ bureau fees from AstraZeneca. Drs. Newton, Wang, and Thiyagarajah report receiving employment and stock ownership with AstraZeneca . Dr. Antonia reports receiving consulting, advisory, and/or speakers’ bureau fees from Bristol-Myers Squibb, Novartis, Merck, AstraZeneca, Boehringer Ingelheim, Cellular Biomedicine Group, and Memgen. Dr. Özgüroğlu declares no conflict of interest.

Funding Information:
Disclosure: Dr. Faivre-Finn reports receiving research funding from AstraZeneca, Elekta, and NIHR Manchester Biomedical Research Centre; and travel support from AstraZeneca, and Elekta. Dr. Vicente reports receiving research funding from AstraZeneca, Pfizer, Merck Sharp & Dohme, and Roche; and honoraria from AstraZeneca, Pfizer, Bristol-Myers Squibb, Merck Sharp & Dohme, and Roche. Dr. Kurata reports receiving research funding from AstraZeneca, Merck Sharp & Dohme, Bristol-Myers Squibb, Novartis, Takeda, and Chugai; and honoraria from AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Ono, Boehringer Ingelheim, Bristol-Myers Squibb, and Chugai. Dr. Planchard reports receiving consulting, advisory, and/or speakers? bureau fees from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche, and Samsung. Dr. Paz-Ares reports receiving consulting, advisory, and/or speakers? bureau fees from Merck Sharp & Dohme, Bristol-Myers Squibb, Roche, AstraZeneca, Eli Lilly, Merck, Novartis, Amgen, Incyte, Takeda, PharmaMar, Ipsen, Blueprint, and Bayer; and has board membership for Altum Sequencing and Genomica. Dr. Vansteenkiste reports receiving research funding from Merck Sharp & Dohme; and consulting, advisory, and/or speakers? bureau fees from AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, Roche, Pfizer, and Bristol-Myers Squibb. Dr. Spigel reports receiving research funding from AstraZeneca, Genentech/Roche, Novartis, Celgene, Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, AbbVie, Foundation Medicine, GlaxoSmithKline, Eli Lilly, Merck, Nektar, Takeda, Amgen, University of Texas Southwestern Medical Center?Simmons Cancer Center, G1 Therapeutics, Neon Therapeutics, Celldex, Clovis Oncology, Daiichi Sankyo, EMD Serono, Astellas Pharma, GRAIL, Transgene, Aeglea Therapeutics, Tesaro, Ipsen, Janssen, BIND Therapeutics, Eisai, and ImClone Systems; and consulting, advisory, and/or speakers? bureau fees from AstraZeneca, Genentech/Roche, Novartis, Celgene, Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, AbbVie, Foundation Medicine, GlaxoSmithKline, Eli Lilly, Merck, Moderna, Nektar, Takeda, Amgen, TRM Oncology, Precision Oncology, Evelo Therapeutics, Illumina, Pharmamar, EMD Serono, Aptitude Health, Dracen Pharmaceuticals, Iksuda Therapeutics, Molecular Templates, Seattle Genetics, TRIPTYCH Health Partners, and Intellisphere. Dr. Garassino reports receiving research funding from Bristol-Myers Squibb, Merck Sharp & Dohme, Roche/Genentech, AstraZeneca, Pfizer, GlaxoSmithKline, Novartis Merck, Incyte, Takeda, Spectrum Pharmaceuticals, and Blueprint Medicines; consulting, advisory, and/or speakers? bureau fees from Bristol-Myers Squibb, Merck Sharp & Dohme, AstraZeneca, Novartis, Takeda, Roche, Tiziana Life Sciences, Sanofi, Celgene, Daiichi Sankyo, Inivata, Incyte, Pfizer, Seattle Genetics, Eli Lilly and Otsuka; travel, accommodation, and expenses from Pfizer, Roche, and AstraZeneca; and honoraria from Merck Sharp & Dohme, AstraZeneca, GlaxoSmithKline, Takeda, Roche, Bristol-Myers Squibb. Dr. Reck reports receiving consulting, advisory, and/or speakers? bureau fees from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Samsung. Dr. Senan reports receiving research funding from AstraZeneca, Varian Medical Systems, and ViewRay, Inc.; consultancy, advisory, and/or speakers? bureau fees from AstraZeneca, Celgene, Merck Sharp & Dohme, Eli Lilly, and Varian Medical Systems. Dr. Naidoo reports receiving research funding from AstraZeneca, Merck, and Roche/Genentech; consulting, advisory, and/or speakers? bureau fees from Bristol-Myers Squibb, AstraZeneca, and Roche/Genentech; travel, accommodations, and expenses from Bristol-Myers Squibb and AstraZeneca. Dr. Rimner reports receiving research funding from AstraZeneca, Varian Medical Systems, Merck, Boehringer Ingelheim, and Pfizer; travel, accommodations, and expenses from AstraZeneca, Merck, Research to Practice, Cybrexa, and More Health; and other fees from Elekta. Dr. Wu reports receiving research funding from AstraZeneca, Bristol-Myers Squibb, and Pfizer; and consulting, advisory, and/or speakers? bureau fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Pfizer, and Sanofi. Dr. Gray reports receiving research funding from Genentech, Merck, Bristol-Myers Squibb, Regeneron, Eli Lilly, Merck KGA, Novartis and Boehringer Ingelheim; and consulting, advisory, and/or speakers? bureau fees from AstraZeneca, Takeda, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck KGA, Novartis, and Merck. Dr. Lee reports receiving consulting, advisory, and/or speakers? bureau fees from Bristol-Myers Squibb, Merck Sharp & Dohme, AstraZeneca, and Pfizer. Dr. Cho reports receiving research funding from Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, and Merck Sharp & Dohme; consulting, advisory, and/or speakers? bureau fees from Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda and Merck Sharp & Dohme; and stock ownership in TheraCanVac, Inc. Dr. Kato reports receiving research funding from AstraZeneca, AbbVie, Amgen, Bristol-Myers Squibb, Chugai, Eli Lilly, Merck, Merck Sharp & Dohme, Novartis, Ono, Pfizer, Taiho, Astellas, Kyorin, Kyowa-Kirin and Regeneron; and consulting, advisory, and/or speakers? bureau fees from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Chugai, Eli Lilly, Merck, Merck Sharp & Dohme, Novartis, Ono, Pfizer, Taiho, Boehringer Ingelheim, Daiichi Sankyo, F. Hoffman-La Roche, Nippon Kayaku, Nitto Denko, Shionogi, Sumitomo Dainippon, and Takeda. Dr. de Wit reports receiving consulting, advisory, and/or speakers? bureau fees from AstraZeneca. Drs. Newton, Wang, and Thiyagarajah report receiving employment and stock ownership with AstraZeneca. Dr. Antonia reports receiving consulting, advisory, and/or speakers? bureau fees from Bristol-Myers Squibb, Novartis, Merck, AstraZeneca, Boehringer Ingelheim, Cellular Biomedicine Group, and Memgen. Dr. ?zg?ro?lu declares no conflict of interest.

Funding Information:
This study (NCT02125461) was sponsored by AstraZeneca. Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Aaron Korpal, PhD, of Cirrus Communications (Manchester, United Kingdom), an Ashfield company, and was funded by AstraZeneca. Dr. Faivre-Finn is supported by a grant from the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre. Dr. Rimner is supported, in part, by a grant from the National Institutes of Health/National Cancer Institute Cancer Center (support grant: P30 CA008748).

Publisher Copyright:
© 2021 International Association for the Study of Lung Cancer

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine

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