Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer

Author(s): David R. Spigel, MD¹; Corinne Faivre-Finn, MD, PhD²; Jhanelle E. Gray, MD³; David Vicente, MD⁴; David Planchard, MD, PhD⁵; Luis Paz-Ares, MD, PhD⁶; Johan F. Vansteenkiste, MD, PhD⁷; Marina C. Garassino, MD^8,9; Rina Hui, PhD¹⁰; Xavier Quantin, MD, PhD¹¹; Andreas Rimner, MD¹²; Yi-Long Wu, MD¹³; Mustafa Özgüroğlu, MD¹⁴; Ki H. Lee, MD¹⁵; Terufumi Kato, MD¹⁶; Maike de Wit, MD, PhD¹⁷; Takayasu Kurata, MD¹⁸; Martin Reck, MD, PhD¹⁹; Byoung C. Cho, MD, PhD²⁰; Suresh Senan, PhD²¹; Jarushka Naidoo, MBBCH, MHS²²; Helen Mann, MSc²³; Michael Newton, PharmD²⁴; Piruntha Thiyagarajah, MD²³; and Scott J. Antonia, MD, PhD³ on behalf of the PACIFIC Investigators

Source: DOI: 10.1200/JCO.21.01308 Journal of Clinical Oncology 40, no. 12 (April 20, 2022) 1301-1311.

Dr. Lucio Gordan's Thoughts

Remarkable study, practice-changing, showing a significant improvement in PFS and OS at 5-years. After initial learning phase insofar as management of pulmonary toxicity from IO Rx, adoption of such therapy hopefully continues to increase from historical baseline.

PURPOSE

The phase III PACIFIC trial compared durvalumab with placebo in patients with unresectable, stage III non–small-cell lung cancer and no disease progression after concurrent chemoradiotherapy. Consolidation durvalumab was associated with significant improvements in the primary end points of overall survival (OS; stratified hazard ratio [HR], 0.68; 95% CI, 0.53 to 0.87; P = .00251) and progression-free survival (PFS [blinded independent central review; RECIST v1.1]; stratified HR, 0.52; 95% CI, 0.42 to 0.65; P < .0001), with manageable safety. We report updated, exploratory analyses of survival, approximately 5 years after the last patient was randomly assigned.

METHODS

Patients with WHO performance status 0 or 1 (any tumor programmed cell death-ligand 1 status) were randomly assigned (2:1) to durvalumab (10 mg/kg intravenously; administered once every 2 weeks for 12 months) or placebo, stratified by age, sex, and smoking history. Time-to-event end point analyses were performed using stratified log-rank tests. Medians and landmark survival rates were estimated using the Kaplan-Meier method.

RESULTS

Seven hundred and nine of 713 randomly assigned patients received durvalumab (473 of 476) or placebo (236 of 237). As of January 11, 2021 (median follow-up, 34.2 months [all patients]; 61.6 months [censored patients]), updated OS (stratified HR, 0.72; 95% CI, 0.59 to 0.89; median, 47.5 v 29.1 months) and PFS (stratified HR, 0.55; 95% CI, 0.45 to 0.68; median, 16.9 v 5.6 months) remained consistent with the primary analyses. Estimated 5-year rates (95% CI) for durvalumab and placebo were 42.9% (38.2 to 47.4) versus 33.4% (27.3 to 39.6) for OS and 33.1% (28.0 to 38.2) versus 19.0% (13.6 to 25.2) for PFS.

CONCLUSION

These updated analyses demonstrate robust and sustained OS and durable PFS benefit with durvalumab after chemoradiotherapy. An estimated 42.9% of patients randomly assigned to durvalumab remain alive at 5 years and 33.1% of patients randomly assigned to durvalumab remain alive and free of disease progression, establishing a new benchmark for standard of care in this setting.

Author Affiliations

¹Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN ²The University of Manchester and The Christie NHS Foundation Trust, Manchester, United Kingdom ³H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL ⁴Hospital Universitario Virgen Macarena, Seville, Spain ⁵Department of Medical Oncology, Thoracic Unit, Gustave Roussy, Villejuif, France ⁶Universidad Complutense, CiberOnc, CNIO and Hospital Universitario 12 de Octubre, Madrid, Spain ⁷University Hospitals KU Leuven, Leuven, Belgium ⁸Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy ⁹Department of Hematology/Oncology, The University of Chicago, Chicago, IL ¹⁰Westmead Hospital and the University of Sydney, Sydney, New South Wales, Australia ¹¹Montpellier Cancer Institute (ICM) and Montpellier Cancer Research Institute (IRCM), INSERM U1194, University of Montpellier, Montpellier, France ¹²Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY ¹³Department of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China ¹⁴Istanbul University—Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey ¹⁵Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Republic of Korea ¹⁶Kanagawa Cancer Center, Yokohama, Japan ¹⁷Vivantes Klinikum Neukölln, Berlin, Germany ¹⁸Department of Thoracic Oncology, Kansai Medical University Hospital, Osaka, Japan ¹⁹Lung Clinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany ²⁰Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea ²¹Department of Radiation Oncology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands ²²Sidney Kimmel Comprehensive Cancer Center and Bloomberg-Kimmel Institute for Cancer Immunotherapy at John Hopkins University, Baltimore, MD ²³AstraZeneca, Cambridge, United Kingdom ²⁴AstraZeneca, Gaithersburg, MD

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