Corinne Faivre-Finn1, David R Spigel2, Suresh Senan3, Corey Langer4, Bradford A Perez5, Mustafa Özgüroğlu6, Davey Daniel2, Augusto Villegas7, David Vicente8, Rina Hui9, Shuji Murakami10, Luis Paz-Ares11, Helen Broadhurst12, Catherine Wadsworth13, Phillip A Dennis14, Scott J Antonia5. 1. The University of Manchester, Manchester, UK; The Christie NHS Foundation Trust, Manchester, UK. Electronic address: corinne.finn@nhs.net. 2. Tennessee Oncology, Chattanooga, TN, USA; Sarah Cannon Research Institute, Nashville, TN, USA. 3. Department of Radiation Oncology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands. 4. Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. 5. H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. 6. Istanbul University - Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey. 7. Cancer Specialists of North Florida, Jacksonville, FL, USA. 8. Hospital Universitario Virgen Macarena, Seville, Spain. 9. Westmead Hospital and the University of Sydney, Sydney, NSW, Australia. 10. Kanagawa Cancer Center, Yokohama, Japan. 11. Hospital Universitario 12 de Octubre, Lung Cancer Unit CNIO-H12o, CiberOnc and Universidad Complutense, Madrid, Spain. 12. Plus-Project Ltd, Alderley Park, UK. 13. AstraZeneca, Alderley Park, UK. 14. AstraZeneca, Gaithersburg, MD, USA.
Abstract
INTRODUCTION: The PACIFIC trial demonstrated that durvalumab significantly improved progression-free and overall survival (PFS/OS), versus placebo, in patients with Stage III NSCLC and stable or responding disease following concurrent, platinum-based chemoradiotherapy (CRT). A range of CT and RT regimens were permitted, and used, in the trial. We report post-hoc, exploratory analyses of clinical outcomes from PACIFIC according to CRT-related variables. METHODS: Patients were randomized 2:1 (1-42 days post-CRT) to up to 12 months durvalumab (10 mg/kg intravenously every 2 weeks) or placebo. Efficacy and safety were analyzed in patient subgroups defined by the following baseline variables: platinum-based CT (cisplatin/carboplatin); vinorelbine, etoposide, or taxane-based CT (all yes/no); total RT dose (<60 Gy/60-66 Gy/>66 Gy); time from last RT dose to randomization (<14 days/≥14 days); and use of pre-CRT induction CT (yes/no). Treatment effects for time-to-event endpoints were estimated by hazard ratios (HRs) from unstratified Cox-proportional-hazards models. RESULTS: Overall, 713 patients were randomized, of whom 709 received treatment in either the durvalumab (n/N = 473/476) or placebo arms (n/N = 236/237). Durvalumab improved PFS, versus placebo, across all subgroups (median follow up, 14.5 months; HR range, 0.34-0.63). Durvalumab improved OS across most subgroups (median follow up, 25.2 months; HR range, 0.35-0.86); however, the 95 % confidence interval (CI) of the estimated treatment effect crossed one for the subgroups of patients who received induction CT (HR, 0.78 [95 % CI, 0.51-1.20]); carboplatin (0.86 [0.60-1.23]); vinorelbine (0.79 [0.49-1.27]); and taxane-based CT (0.73 [0.51-1.04]); and patients who were randomized ≥14 days post-RT (0.81 [0.62-1.06]). Safety was broadly similar across the CRT subgroups. CONCLUSION:Durvalumab prolonged PFS and OS irrespective of treatment variables related to prior CRT to which patients with Stage III NSCLC had previously stabilized or responded. Limited patient numbers and imbalances in baseline factors in each subgroup preclude robust conclusions.
RCT Entities:
INTRODUCTION: The PACIFIC trial demonstrated that durvalumab significantly improved progression-free and overall survival (PFS/OS), versus placebo, in patients with Stage III NSCLC and stable or responding disease following concurrent, platinum-based chemoradiotherapy (CRT). A range of CT and RT regimens were permitted, and used, in the trial. We report post-hoc, exploratory analyses of clinical outcomes from PACIFIC according to CRT-related variables. METHODS:Patients were randomized 2:1 (1-42 days post-CRT) to up to 12 months durvalumab (10 mg/kg intravenously every 2 weeks) or placebo. Efficacy and safety were analyzed in patient subgroups defined by the following baseline variables: platinum-based CT (cisplatin/carboplatin); vinorelbine, etoposide, or taxane-based CT (all yes/no); total RT dose (<60 Gy/60-66 Gy/>66 Gy); time from last RT dose to randomization (<14 days/≥14 days); and use of pre-CRT induction CT (yes/no). Treatment effects for time-to-event endpoints were estimated by hazard ratios (HRs) from unstratified Cox-proportional-hazards models. RESULTS: Overall, 713 patients were randomized, of whom 709 received treatment in either the durvalumab (n/N = 473/476) or placebo arms (n/N = 236/237). Durvalumab improved PFS, versus placebo, across all subgroups (median follow up, 14.5 months; HR range, 0.34-0.63). Durvalumab improved OS across most subgroups (median follow up, 25.2 months; HR range, 0.35-0.86); however, the 95 % confidence interval (CI) of the estimated treatment effect crossed one for the subgroups of patients who received induction CT (HR, 0.78 [95 % CI, 0.51-1.20]); carboplatin (0.86 [0.60-1.23]); vinorelbine (0.79 [0.49-1.27]); and taxane-based CT (0.73 [0.51-1.04]); and patients who were randomized ≥14 days post-RT (0.81 [0.62-1.06]). Safety was broadly similar across the CRT subgroups. CONCLUSION:Durvalumab prolonged PFS and OS irrespective of treatment variables related to prior CRT to which patients with Stage III NSCLC had previously stabilized or responded. Limited patient numbers and imbalances in baseline factors in each subgroup preclude robust conclusions.
Authors: Diego L Kaen; Nicolas Minatta; Alessandro Russo; Umberto Malapelle; Diego de Miguel-Pérez; Christian Rolfo Journal: Adv Exp Med Biol Date: 2021 Impact factor: 2.622
Authors: Luis E Raez; Oscar Arrieta; Diego F Chamorro; Pamela Denisse Soberanis-Piña; Luis Corrales; Claudio Martín; Mauricio Cuello; Suraj Samtani; Gonzalo Recondo; Luis Mas; Zyanya Lucia Zatarain-Barrón; Alejandro Ruíz-Patiño; Juan Esteban García-Robledo; Camila Ordoñez-Reyes; Elvira Jaller; Franco Dickson; Leonardo Rojas; Christian Rolfo; Rafael Rosell; Andrés F Cardona Journal: Front Oncol Date: 2022-07-12 Impact factor: 5.738
Authors: David R Spigel; Corinne Faivre-Finn; Jhanelle E Gray; David Vicente; David Planchard; Luis Paz-Ares; Johan F Vansteenkiste; Marina C Garassino; Rina Hui; Xavier Quantin; Andreas Rimner; Yi-Long Wu; Mustafa Özgüroğlu; Ki H Lee; Terufumi Kato; Maike de Wit; Takayasu Kurata; Martin Reck; Byoung C Cho; Suresh Senan; Jarushka Naidoo; Helen Mann; Michael Newton; Piruntha Thiyagarajah; Scott J Antonia Journal: J Clin Oncol Date: 2022-02-02 Impact factor: 50.717