D Planchard1, N Reinmuth2, S Orlov3, J R Fischer4, S Sugawara5, S Mandziuk6, D Marquez-Medina7, S Novello8, Y Takeda9, R Soo10, K Park11, M McCleod12, S L Geater13, M Powell14, R May14, U Scheuring15, P Stockman15, D Kowalski16. 1. Gustave Roussy, Department of Medical Oncology, Thoracic Group, Villejuif, France. Electronic address: David.PLANCHARD@gustaveroussy.fr. 2. Asklepios Lung Clinic, Munich-Gauting, Germany. 3. Pavlov State Medical University, St Petersburg, Russia. 4. Lungenklinik Loewenstein, Löwenstein, Germany. 5. Sendai Kousei Hospital, Sendai, Japan. 6. Medical University of Lublin, Lublin, Poland. 7. Arnau de Vilanova University Hospital, Lleida, Spain. 8. Department of Oncology, University of Turin, Azienda Ospedaliero-Universitaria San Luigi, Orbassano, Italy. 9. National Center for Global Health and Medicine, Tokyo, Japan. 10. National University Hospital, Singapore. 11. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. 12. Florida Cancer Specialists, Fort Myers, USA. 13. Prince of Songkla University, Songkhla, Thailand. 14. AstraZeneca, Gaithersburg, USA. 15. AstraZeneca, Cambridge, UK. 16. Maria Sklodowska-Curie Institute of Oncology, Warsaw, Poland.
Abstract
BACKGROUND: Many patients with metastatic non-small-cell lung cancer (mNSCLC) experience disease progression after first- and second-line treatment; more treatment options are required for these patients. ARCTIC, a phase III, randomized, open-label study, assessed durvalumab ± tremelimumab versus standard of care (SoC) as ≥ third-line treatment of mNSCLC. PATIENTS AND METHODS: ARCTIC comprised two independent sub-studies. Study A: 126 patients with ≥25% of tumor cells (TCs) expressing programmed cell death ligand-1 (PD-L1) were randomized (1 : 1) to durvalumab [up to 12 months 10 mg/kg every 2 weeks (q2w)] or SoC. Study B: 469 patients with PD-L1 TC <25% were randomized (3 : 2 : 2 : 1) to durvalumab + tremelimumab (12 weeks durvalumab 20 mg/kg + tremelimumab 1 mg/kg q4w then 34 weeks durvalumab 10 mg/kg q2w), SoC, durvalumab (up to 12 months 10 mg/kg q2w), or tremelimumab (24 weeks 10 mg/kg q4w then 24 weeks q12w). Primary end points: overall survival (OS) and progression-free survival (PFS) for durvalumab versus SoC (study A; descriptive only) and durvalumab + tremelimumab versus SoC (study B). RESULTS: Study A: median OS 11.7 (durvalumab) versus 6.8 (SoC) months {hazard ratio (HR) 0.63 [95% confidence interval (CI), 0.42-0.93]}; median PFS 3.8 (durvalumab) versus 2.2 (SoC) months [HR 0.71 (95% CI, 0.49-1.04)]. Study B: median OS 11.5 (durvalumab + tremelimumab) versus 8.7 (SoC) months [HR 0.80 (95% CI, 0.61-1.05); P = 0.109]. Median PFS of 3.5 months for both groups [HR 0.77 (95% CI, 0.59-1.01); P = 0.056]. Treatment-related grade 3/4 adverse events: 9.7% (durvalumab) and 44.4% (SoC; study A) and 22.0% (durvalumab + tremelimumab) and 36.4% (SoC; study B). CONCLUSIONS: In heavily pretreated patients with mNSCLC, durvalumab demonstrated clinically meaningful improvements in OS and PFS versus SoC (patients with PD-L1 TC ≥25%); numerical improvements in OS and PFS for durvalumab + tremelimumab versus SoC were observed (patients with PD-L1 TC <25%). Safety profiles were consistent with previous studies. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02352948.
BACKGROUND: Many patients with metastatic non-small-cell lung cancer (mNSCLC) experience disease progression after first- and second-line treatment; more treatment options are required for these patients. ARCTIC, a phase III, randomized, open-label study, assessed durvalumab ± tremelimumab versus standard of care (SoC) as ≥ third-line treatment of mNSCLC. PATIENTS AND METHODS: ARCTIC comprised two independent sub-studies. Study A: 126 patients with ≥25% of tumor cells (TCs) expressing programmed cell death ligand-1 (PD-L1) were randomized (1 : 1) to durvalumab [up to 12 months 10 mg/kg every 2 weeks (q2w)] or SoC. Study B: 469 patients with PD-L1 TC <25% were randomized (3 : 2 : 2 : 1) to durvalumab + tremelimumab (12 weeks durvalumab 20 mg/kg + tremelimumab 1 mg/kg q4w then 34 weeks durvalumab 10 mg/kg q2w), SoC, durvalumab (up to 12 months 10 mg/kg q2w), or tremelimumab (24 weeks 10 mg/kg q4w then 24 weeks q12w). Primary end points: overall survival (OS) and progression-free survival (PFS) for durvalumab versus SoC (study A; descriptive only) and durvalumab + tremelimumab versus SoC (study B). RESULTS: Study A: median OS 11.7 (durvalumab) versus 6.8 (SoC) months {hazard ratio (HR) 0.63 [95% confidence interval (CI), 0.42-0.93]}; median PFS 3.8 (durvalumab) versus 2.2 (SoC) months [HR 0.71 (95% CI, 0.49-1.04)]. Study B: median OS 11.5 (durvalumab + tremelimumab) versus 8.7 (SoC) months [HR 0.80 (95% CI, 0.61-1.05); P = 0.109]. Median PFS of 3.5 months for both groups [HR 0.77 (95% CI, 0.59-1.01); P = 0.056]. Treatment-related grade 3/4 adverse events: 9.7% (durvalumab) and 44.4% (SoC; study A) and 22.0% (durvalumab + tremelimumab) and 36.4% (SoC; study B). CONCLUSIONS: In heavily pretreated patients with mNSCLC, durvalumab demonstrated clinically meaningful improvements in OS and PFS versus SoC (patients with PD-L1 TC ≥25%); numerical improvements in OS and PFS for durvalumab + tremelimumab versus SoC were observed (patients with PD-L1 TC <25%). Safety profiles were consistent with previous studies. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02352948.
Authors: Jonathan D Schoenfeld; Anita Giobbie-Hurder; Srinika Ranasinghe; Katrina Z Kao; Ana Lako; Junko Tsuji; Yang Liu; Ryan C Brennick; Ryan D Gentzler; Carrie Lee; Joleen Hubbard; Susanne M Arnold; James L Abbruzzese; Salma K Jabbour; Nataliya V Uboha; Kevin L Stephans; Jennifer M Johnson; Haeseong Park; Liza C Villaruz; Elad Sharon; Howard Streicher; Mansoor M Ahmed; Hayley Lyon; Carrie Cibuskis; Niall Lennon; Aashna Jhaveri; Lin Yang; Jennifer Altreuter; Lauren Gunasti; Jason L Weirather; Raymond H Mak; Mark M Awad; Scott J Rodig; Helen X Chen; Catherine J Wu; Arta M Monjazeb; F Stephen Hodi Journal: Lancet Oncol Date: 2022-01-13 Impact factor: 41.316
Authors: Aaron C Tan; Stephen J Bagley; Patrick Y Wen; Michael Lim; Michael Platten; Howard Colman; David M Ashley; Wolfgang Wick; Susan M Chang; Evanthia Galanis; Alireza Mansouri; Simon Khagi; Minesh P Mehta; Amy B Heimberger; Vinay K Puduvalli; David A Reardon; Solmaz Sahebjam; John Simes; Scott J Antonia; Don Berry; Mustafa Khasraw Journal: J Immunother Cancer Date: 2021-07 Impact factor: 13.751