Corinne Faivre-Finn1, David Vicente2, Takayasu Kurata3, David Planchard4, Luis Paz-Ares5, Johan F Vansteenkiste6, David R Spigel7, Marina C Garassino8, Martin Reck9, Suresh Senan10, Jarushka Naidoo11, Andreas Rimner12, Yi-Long Wu13, Jhanelle E Gray14, Mustafa Özgüroğlu15, Ki H Lee16, Byoung C Cho17, Terufumi Kato18, Maike de Wit19, Michael Newton20, Lu Wang20, Piruntha Thiyagarajah21, Scott J Antonia14. 1. The University of Manchester, Manchester, United Kingdom; The Christie NHS Foundation Trust, Manchester, United Kingdom. Electronic address: corinne.finn@nhs.net. 2. Department of Medical Oncology, Hospital Universitario Virgen Macarena, Seville, Spain. 3. Department of Internal Medicine, Kansai Medical University Hospital, Hirakata, Japan. 4. Department of Medical Oncology, Thoracic Unit, Gustave Roussy, Villejuif, France. 5. CiberOnc, Universidad Complutense, Madrid, Spain; Centro Nacional De Investigaciones Oncologicas (CNIO), Hospital Universitario 12 de Octubre, Madrid, Spain. 6. Department of Chronic Disease and Metabolism, University Hospitals KU Leuven, Leuven, Belgium. 7. Sarah Cannon Research Institute/Tennessee Oncology, Nashville, Tennessee. 8. Division of Medical Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milan, Italy. 9. Lung Clinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany. 10. Department of Radiation Oncology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands. 11. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland; Bloomberg-Kimmel Institute for Cancer Immunotherapy at John Hopkins University, Baltimore, Maryland. 12. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. 13. Department of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China. 14. Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. 15. Division of Medical Oncology, Department of Internal Medicine, Cerrahpaşa School of Medicine, Istanbul University - Cerrahpaşa, Istanbul, Turkey. 16. Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea. 17. Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea. 18. Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan. 19. Department of Hematology, Oncology, and Palliative Medicine, Vivantes Klinikum Neukölln, Berlin, Germany. 20. Department of Clinical Oncology, AstraZeneca, Gaithersburg, Maryland. 21. Department of Clinical Oncology, AstraZeneca, Cambridge, United Kingdom.
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%).
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%).
Authors: Edward Chandy; Adam Szmul; Alkisti Stavropoulou; Joseph Jacob; Catarina Veiga; David Landau; James Wilson; Sarah Gulliford; John D Fenwick; Maria A Hawkins; Crispin Hiley; Jamie R McClelland Journal: Cancers (Basel) Date: 2022-02-14 Impact factor: 6.639
Authors: John M Varlotto; Zhuoxin Sun; Bonnie Ky; Jenica Upshaw; Sharyn I Katz; Thomas J Fitzgerald; Heather Wakelee; Maximilian Diehn; David A Mankoff; Christine Lovely; Chandra Belani; Kurt Oettel; Gregory Masters; Suresh Ramalingam; Nathan A Pennell Journal: Oncologist Date: 2021-03-11
Authors: Nicola Principe; Joel Kidman; Richard A Lake; Willem Joost Lesterhuis; Anna K Nowak; Alison M McDonnell; Jonathan Chee Journal: Front Oncol Date: 2021-04-27 Impact factor: 6.244
Authors: Kevin X Liu; Kailan Sierra-Davidson; Kevin Tyan; Lawrence T Orlina; J Paul Marcoux; Benjamin H Kann; David E Kozono; Raymond H Mak; Abby White; Lisa Singer Journal: Radiother Oncol Date: 2021-10-22 Impact factor: 6.280