Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2017

Clinical activity, patient-reported outcomes, and safety with durvalumab after chemoradiation in locally advanced, unresectable NSCLC: PACIFIC study (#218)

Rina Hui 1 , Mustafa Özgüroğlu 2 , Augusto Villegas 3 , Davey Daniel 4 , David Vincente 5 , Shuji Murakami 6 , Takashi Yokoi 7 , Alberto Chiappori 8 , Ki Hyeong Lee 9 , Maike de Wit 10 , Byoung Cul Cho 11 , Jhanelle E Gray 8 , Anna Ryden 12 , Louis Viviers 13 , Lynne Poole 14 , Phillip A Dennis 15 , Scott J Antonia 8
  1. Westmead Hospital and the University of Sydney, Sydney, NSW, Australia
  2. Istanbul University, Cerrahpasa School of Medicine , Istanbul, Turkey
  3. Cancer Specialists of North Florida, Jacksonville, Florida, USA
  4. Sarah Cannon Research Institute, Nashville, and Tennessee Oncology, Chattanooga, Tennessee, USA
  5. Hospital Universitario Virgen Macarena, Seville, Spain
  6. Kanagawa Cancer Center, Yokohama, Japan
  7. Kansai Medical University Hospital, Hirakata, Japan
  8. H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
  9. Chungbuk National University Hospital, Cheongju-si, Korea
  10. Vivantes Klinikum Neukoelln, Berlin, Germany
  11. Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
  12. AstraZeneca, Gothenburg, Sweden
  13. QuintilesIMS, Saint Ouen Cedex, France
  14. AstraZeneca, Cambridge, UK
  15. AstraZeneca, Gaithersburg, MD, USA

Background: Most patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) progress despite standard platinum-based, concurrent chemoradiation therapy (cCRT). We report interim results for clinical activity, patient-reported outcomes (PROs), and safety from a global, Phase 3 study (NCT02125461) of durvalumab as consolidation therapy in Stage III patients.

Methods: In this double-blind study, patients with WHO PS 0/1 (any PD-L1 status) who received ≥2 platinum-based cCRT cycles without progression were randomized (2:1) 1–42 days post-cCRT to durvalumab 10 mg/kg IV Q2W or placebo 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), PROs (EORTC QLQ-C30 and QLQ-LC13) and safety.

Results: Of 713 randomized patients, 709 received treatment (durvalumab, n=473; placebo, n=236). Baseline characteristics were well balanced. At 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<0.0001). 12- and 18-month PFS rates were 55.9% versus 35.3% and 44.2% versus 27.0%, respectively. ORR was higher (28.4% vs 16.0%; P<0.001) and median DoR longer (not reached vs 13.8 months) with durvalumab. Median TTDM was longer with durvalumab (23.2 vs 14.6 months; stratified HR 0.52, 95% CI, 0.39–0.69; P<0.0001). OS data were immature. Comparing durvalumab with placebo, grade 3/4 AEs occurred in 29.9% and 26.1%; most common was pneumonia (4.4% vs 3.8%). 15.4% and 9.8% discontinued due to AEs. PROs will be presented.

Conclusions: Durvalumab demonstrated a statistically significant, robust improvement in PFS, supported by secondary endpoints. No new safety signals were identified.