Special Session

SS 22 - Late-Breaking Abstracts Special Session

LBA10 - PACIFIC: Overall Survival with Durvalumab versus Placebo after Chemoradiotherapy in Stage III NSCLC

Tuesday, October 23
8:05 AM - 8:15 AM
Location: Room 007 C/D

PACIFIC: Overall Survival with Durvalumab versus Placebo after Chemoradiotherapy in Stage III NSCLC
D. Raben1, C. Faivre-Finn2, D. Spigel3, D. Daniel3,4, A. Villegas5, D. Vincente6, R. Hui7, J. de Castro Carpeno8, S. Murakami9, L. Paz-Ares10, M. Özgüroğlu11, T. Kurata12, A. Chiappori13, K. H. Lee14, M. de Wit15, L. Poole16, C. Wadsworth17, P. A. Dennis18, and S. J. Antonia13; 1University of Colorado Cancer Center, Aurora, CO, 2Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom, 3Sarah Cannon Research Institute, Nashville, TN, 4Tennessee Oncology, Chattanooga, TN, 5Cancer Specialists of North Florida, Jacksonville, FL, 6Hospital Universitario Virgen Macarena, Sevilla, Spain, 7Westmead Hospital and the University of Sydney, Sydney, Australia, 8Hospital Universitario La Paz, Madrid, Spain, 9Kanagawa Cancer Center, Yokohama, Japan, 10Hospital Universitario 12 de Octubre, CiberOnc, Universidad Complutense and CNIO, Madrid, Spain, 11Istanbul University − Cerrahpasa, Cerrahpasa School of Medicine, Istanbul, Turkey, 12Kansai Medical University Hospital, Hirakata, Japan, 13H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 14Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea, Republic of (South), 15Vivantes Klinikum Neukoelln, Berlin, Germany, 16AstraZeneca, Cambridge, United Kingdom, 17AstraZeneca, Alderley Park, United Kingdom, 18AstraZeneca, Gaithersburg, MD

Purpose/Objective(s): In the global, Phase 3 PACIFIC study (Antonia 2017; NCT02125461), durvalumab significantly improved progression-free survival (PFS) versus placebo in Stage III, unresectable NSCLC patients without progression after concurrent chemoradiotherapy (CRT) (stratified HR, 0.52; 95% CI, 0.42–0.65; P<0.001). This was the first major advance in this disease setting for many years. Here we report the second primary endpoint of overall survival (OS) for PACIFIC.

Materials/Methods: Patients (any PD-L1 tumor status) with WHO PS 0/1 who received ≥2 cycles of platinum-based CRT were randomized (2:1) 1–42 days post-CRT to durvalumab 10 mg/kg IV Q2W or placebo up to 12 months, stratified by age, sex, and smoking history. Primary endpoints were PFS from randomization (blinded independent central review; RECIST v1.1) and OS (interim analysis reported). Secondary endpoints included time to death or distant metastasis (TTDM) and PFS2 (time to second progression) from randomization and safety. Time to first/second subsequent therapy or death (TFST/TSST) were supportive assessments for PFS/PFS2.

Results: Between May 2014 and April 2016, 713 patients were randomized; 709 received treatment (durvalumab, n=473; placebo, n=236). As of March 22, 2018 (data cutoff), median follow-up duration was 25.2 months (range, 0.2–43.1). After discontinuation, 41.0% and 54.0% in the durvalumab and placebo groups received subsequent anticancer therapy; overall, 8.0% and 22.4% received additional immunotherapy. Durvalumab significantly improved OS versus placebo (stratified HR 0.68, 99.73% CI, 0.469–0.997; P=0.00251), with the median not reached (NR; 95% CI, 34.7 months–NR) and 28.7 months (95% CI, 22.9–NR), respectively. Durvalumab improved OS in all pre-specified subgroups. Updated PFS remained similar (stratified HR 0.51, 95% CI, 0.41–0.63), with medians of 17.2 and 5.6 months with durvalumab and placebo, respectively. Durvalumab improved updated TTDM (stratified HR 0.53, 95% CI, 0.41–0.68), and PFS2 (stratified HR 0.58, 95% CI, 0.46–0.73), TFST (stratified HR 0.58, 95% CI, 0.47–0.72) and TSST (stratified HR 0.63, 95% CI, 0.50–0.79). Within the durvalumab and placebo groups, 30.5% and 26.1% had grade 3/4 any-causality AEs, 15.4% and 9.8% discontinued due to AEs, and no new safety signals were identified; any-grade (grade 3/4) pneumonitis/radiation pneumonitis occurred in 33.9% (3.6%) and 24.8% (3.0%). Exploratory analyses characterizing outcome based on features of previous CRT will be presented.

Conclusion: Durvalumab demonstrated statistically significant and clinically meaningful improvement in OS compared with placebo, supported by secondary endpoints such as PFS2. PACIFIC is the first study to show a survival advantage following CRT in this locally advanced NSCLC population, providing compelling evidence for the unprecedented benefit of durvalumab treatment as the standard of care.

Author Disclosure: D. Raben: Honoraria; Nanobiotix, Merck. Consultant; Astra Zeneca, Suvica. Advisory Board; Nanobiotix, Astra Zeneca, Genentech, Merck. C. Faivre-Finn: Research Grant; AZ, Elekta, Merck. Honoraria; Pfizer. Travel Expenses; AZ, Elekta, Pfizer. group memeber; NCRN Lung Cancer Subgroup. group member; British Thoracic Soc Guidelines Cmmtt, Workstream 3, NCRI CTRad, UK Lung SBRR Group. research lead; MCRC Lung Radiotherapy. member; British Thoracic Oncology Grp, Steering Cmmtt, British Thoracic Socity Guidelines Cmmtt, European Respiratory Society, ESMO Lung Cancer Consensus Conference, ESMO clinical practice guidelines, ESMO, Advanced Radiation Technology (ART) Committee, ERS-EACTS-ESTS-ESTRO, ESTRO/ACROP guideline committee. Radiotherapy research lead; CRUK Lung Cancer Centre of Excellence. Clinical expert review panel; Cancer Research UK. Chair; EORTC Lung Group. Early disease Chair of the EORTC Lung Group; EORTC Lung Group. Contact NOCI clinician; Christie Hospital and, EORTC HQ (collaboration). Fellow; European Academy of Cancer Science. cmmtt member; ESTRO, IASLC. D. Spigel: None. A. Villegas: Speaker's Bureau; AstraZeneca, Gilead, Seattle Genetics. D. Vincente: None. R. Hui: Honoraria; MSD, Novartis. Advisory Board; AstraZenec, MSD, Roche, BMS, Novartis. J. de Castro Carpeno: None. L. Paz-Ares: Advisory Board; Lilly, MSD, BMS, AstraZeneca, Novartis, Roche, Incyte, Celgene, Pfizer, Merck, Takeda. M. Özgüroğlu: None. T. Kurata: Research Grant; AstraZeneca. Honoraria; AstraZeneca. A. Chiappori: Research Grant; BMS, Novartis. Speaker's Bureau; Genentech, Takeda, Merck, BI, Celgene. Advisory Board; AstraZeneca, BMS, Novartis. K. Lee: None. M. de Wit: Research Grant; AstraZeneca. Speaker's Bureau; AstraZeneca. L. Poole: Stock Options; AstraZeneca. C. Wadsworth: Stock Options; AstraZeneca. P.A. Dennis: Stock Options; AstraZeneca. S.J. Antonia: Employee; H Lee Moffitt Cancer Center. Research Grant; Novartis. Advisory Board; BMS, Novartis, Merck, CBMG, Boehringer Ingelheim, AstraZeneca/MedImmune, Memgen, FLX Bio.

David Raben, MD, FASTRO

University of Colorado

Disclosure:
Employment
Radiation Oncology, Univ of Colorado Health: Professor: Employee

Compensation
Astra Zeneca: Advisory Board, Consultant; Genentech: Advisory Board; Merck: Advisory Board, Honoraria; Nanobiotix: Advisory Board, Honoraria; Suvica: Consultant

Biography:
David Raben, M.D. is currently faculty at the University of Colorado where he is a board-certified Professor of Radiation Oncology holding the Marsico Endowed Chair for HNC Research. He received a B.A. in Psychology from Duke University in 1985 and then completed his M.D. at Wake Forest University/Bowman Grey School of Medicine in 1990. After graduation, he did his internship at the University of Hawaii and residency in Radiation Oncology at the Johns Hopkins Hospital from 1991-1994, serving as a chief resident in 1994. He took his initial faculty position at the University of Alabama at Birmingham from 1994-1998 before joing the University of Colorado. Dr. Raben has developed expertise over the past 20 years in translational radiation oncology with a focus on delivery of precision drugs and exploration of molecular biomarkers that will enhance the effects of radiation therapy. He serves on the NRG HNC steering committee and translational committee focusing on NCI approved clinical trials devoted to HNC. Dr. Raben also serves on the SWOG GU Steering committee for prostate and bladder cancer. He currently serves as the Developmental Therapeutics co-Chair at the NRG with responsibilities to initiate and implement Phase I trials with radiation and novel drugs. From a research perspective, his focus has been on heavy smoker HNC patients who have high levels of DNA repair capabilities offering approaches that will inhibit DNA repair while studying which biomarkers might predict response. Additional work has focused on the use of TGFb inhibitors as both radioprotectors and to enhance anti-PDL1 inbibition in head and neck models. Recently accepted for publication was the first radiation trial with an anti-EGFR inhibitor and a PARP inhibitor in locally advanced HNC. Dr Raben was named as an ASCO daily News Associate Editor in 2018. He has authored over 150 publications.

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