LBA1_PR - PACIFIC: A double-blind, placebo-controlled Phase III study of durvalumab after chemoradiation therapy (CRT) in patients with Stage III, locally ad...

Date 09 September 2017
Event ESMO 2017 Congress
Session Presidential Symposium I
Topics Non-Small-Cell Lung Cancer, Locally Advanced
Cancer Immunology and Immunotherapy
Lung and other Thoracic Tumours
Presenter Luis Paz-Ares
Citation Annals of Oncology (2017) 28 (suppl_5): v605-v649. 10.1093/annonc/mdx440
Authors L. Paz-Ares1, A. Villegas2, D. Daniel3, D.V. Baz4, S. Murakami5, R. Hui6, T. Yokoi7, A. Chiappori8, K.H. Lee9, M. de Wit10, B.C. Cho11, M. Bourhaba12, X. Quantin13, T. Tokito14, T. Mekhail15, D. Planchard16, H. Jiang17, Y. Huang17, P.A. Dennis17, M. Özgüroğlu18
  • 1Medical Oncology, Hospital Universitario 12 de Octubre, CiberOnc, Universidad Complutense and CNIO, 28041 - Madrid/ES
  • 2Medical Oncology, Cancer Specialists of North Florida, Jacksonville/US
  • 3Sarah Cannon Research Institute, Tennessee Oncology, Chattanooga/US
  • 4Medical Oncology, Hospital Universitario Virgen Macarena, Seville/ES
  • 5Thoracic Oncology, Kanagawa Cancer Center, Yokohama/JP
  • 6Medical Oncology, Westmead Hospital and the University of Sydney, Sydney/AU
  • 7Thoracic Oncology, Kansai Medical University Hospital, Hirakata/JP
  • 8Medical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa/US
  • 9Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju/KR
  • 10Hematology And Oncology, Vivantes Klinikum Neukoelln, Berlin/DE
  • 11Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul/KR
  • 12Medical Oncology, Centre Hospitalier Universitaire de Liège, Liège/BE
  • 13Medical Oncology, CHU Montpellier and ICM Val d'Aurelle, Montpellier/FR
  • 14Internal Medicine, Kurume University Hospital, Kurume/JP
  • 15Hematology And Medical Oncology, Florida Hospital Cancer Institute, Orlando/US
  • 16Medical Oncology, Gustave Roussy, Villejuif/FR
  • 17Immuno-oncology, AstraZeneca, Gaithersburg/US
  • 18Internal Medicine, Istanbul University Cerrahpasa School of Medicine, Istanbul/TR

Abstract

Background

Most patients (pts) with locally advanced, unresectable non-small cell lung cancer (NSCLC) progress despite concurrent chemoradiation therapy (cCRT). Here we report interim results from a global, Phase 3 study (NCT02125461) of the anti-PD-L1 durvalumab as consolidation therapy in Stage III pts without progression following platinum-based cCRT.

Methods

Pts with a WHO performance status 0/1 (any PD-L1 status) who received ≥2 cycles of platinum-based cCRT without progression were randomized (2:1) 1–42 days post-cCRT to receive durvalumab 10 mg/kg IV Q2W or placebo for up to 12 months, stratified by age, sex, and smoking history. Co-primary endpoints were progression-free survival (PFS; blinded independent central review, RECIST v1.1) and overall survival (OS). Secondary endpoints included 12- and 18-month PFS rates, objective response rate (ORR), duration of response (DoR), time to death or distant metastasis (TTDM) and safety.

Results

Between May 2014 and April 2016, 713 pts were randomized of whom 709 received consolidated treatment (durvalumab, n = 473; placebo, n = 236). Baseline characteristics were well balanced. As of Feb 13, 2017 (data cutoff), median follow-up was 14.5 months. Median PFS from randomization was significantly longer with durvalumab (16.8 months, 95% CI, 13.0–18.1) versus placebo (5.6 months, 95% CI, 4.6–7.8; stratified HR 0.52, 95% CI, 0.42–0.65; P 

Conclusions

Durvalumab demonstrated significant and clinically meaningful improvement in PFS, which was supported by secondary endpoints, and was well tolerated. Durvalumab is a promising therapeutic option in this setting.

(Dr. Scott J. Antonia of H. Lee Moffitt Cancer Center and Research Institute is the lead author for this study. Dr. Luis Paz-Ares is presenting on his behalf).

Clinical trial identification

NCT02125461 (April 25, 2014)

Legal entity responsible for the study

AstraZeneca

Funding

AstraZeneca

Disclosure

L. Paz-Ares: Consultancy fees from AstraZeneca, Bristol-Myers Squibb, Merck Sharp and Dohme, Pfizer, Roche, Lilly, Boehringer Ingelheim, Novartis, and Ariad. A. Villegas: Speaker honoraria from Celgene, Alexion, and Bristol-Myers Squibb. R. Hui: Advisory board fees from AstraZeneca, Merck Sharp and Dohme, and Novartis, and a speaker honorarium from Merck Sharp and Dohme. A. Chiappori: Speaker honoraria from Genentech, Merck, Takeda, Novartis, Pfizer, Boehringer Ingelheim, and Celgene, and research support from Novartis and Bristol-Myers Squibb. M. de Wit: A speaker honorarium from AstraZeneca. T. Mekhail: A speaker honorarium and research support from AstraZeneca. D. Planchard: Advisory board fees from AstraZeneca, Bristol-Myers Squibb, Merck Sharp and Dohme, Pfizer, Novartis, Roche, Lilly, and Boehringer Ingelheim. H. Jiang, Y. Huang, P.A. Dennis: Full-time employee of AstraZeneca with stock ownership. All other authors have declared no conflicts of interest.