E E Vokes1, N Ready2, E Felip3, L Horn4, M A Burgio5, S J Antonia6, O Arén Frontera7, S Gettinger8, E Holgado9, D Spigel10, D Waterhouse11, M Domine12, M Garassino13, L Q M Chow14, G Blumenschein15, F Barlesi16, B Coudert17, J Gainor18, O Arrieta19, J Brahmer20, C Butts21, M Steins22, W J Geese23, A Li23, D Healey23, L Crinò5. 1. Department of Medicine, University of Chicago Medicine & Biological Sciences, Chicago, USA. Electronic address: evokes@medicine.bsd.uchicago.edu. 2. Department of Medicine, Duke University Medical Center, Durham, USA. 3. Lung Cancer Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain. 4. Thoracic Oncology Program, Vanderbilt-Ingram Cancer Center, Nashville, USA. 5. Medical Oncology Unit, Istituto Scientifico Romagnolo Per lo Studio e la Cura dei Tumori (IRST) IRCSS, Meldola, Italy. 6. Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, USA. 7. Oncologia Medica, Centro Internacional de Estudios Clinicos, Santiago, Chile, USA. 8. Department of Internal Medicine, Yale Comprehensive Cancer Center, New Haven, USA. 9. Department of Medicine, Hospital De Madrid, Madrid, Spain. 10. Research Consortium, Sarah Cannon Research Institute, Nashville, USA; Tennessee Oncology, PLLC, Nashville, USA. 11. Department of Medical Oncology, OHC (Oncology Hematology Care), Cincinnati, USA; US Oncology, Cincinnati, USA. 12. Department of Medical Oncology, Fundación Jiménez Díaz, Madrid, Spain. 13. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 14. Department of Medicine, University of Washington, Seattle, USA. 15. Department of Thoracic/Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, USA. 16. Multidisciplinary Oncology & Therapeutic Innovations Departmen, Aix-Marseille Université, Assistance Publique Hôpitaux de Marseille, Marseille, France. 17. Department of Medical Oncology, Centre Georges François Leclerc, Dijon, France. 18. Cancer Center, Massachusetts General Hospital, Boston, USA. 19. Thoracic Oncology Unit and Laboratory, Instituto Nacional de Cancerología, Mexico City, Mexico. 20. Thoracic Oncology Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, USA. 21. Department of Oncolog, Division of Medical Oncology, Cross Cancer Institute, Edmonton, Canada. 22. Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany. 23. Immuno-Oncology, Bristol-Myers Squibb, Princeton, USA.
Abstract
Background: Long-term data with immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are limited. Two phase III trials demonstrated improved overall survival (OS) and a favorable safety profile with the anti-programmed death-1 antibody nivolumab versus docetaxel in patients with previously treated advanced squamous (CheckMate 017) and nonsquamous (CheckMate 057) NSCLC. We report results from ≥3 years' follow-up, including subgroup analyses of patients with liver metastases, who historically have poorer prognosis among patients with NSCLC. Patients and methods: Patients were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks) until progression or discontinuation. The primary end point of each study was OS. Patients with baseline liver metastases were pooled across studies by treatment for subgroup analyses. Results: After 40.3 months' minimum follow-up in CheckMate 017 and 057, nivolumab continued to show an OS benefit versus docetaxel: estimated 3-year OS rates were 17% [95% confidence interval (CI), 14% to 21%] versus 8% (95% CI, 6% to 11%) in the pooled population with squamous or nonsquamous NSCLC. Nivolumab was generally well tolerated, with no new safety concerns identified. Of 854 randomized patients across both studies, 193 had baseline liver metastases. Nivolumab resulted in improved OS compared with docetaxel in patients with liver metastases (hazard ratio, 0.68; 95% CI, 0.50-0.91), consistent with findings from the overall pooled study population (hazard ratio, 0.70; 95% CI, 0.61-0.81). Rates of treatment-related hepatic adverse events (primarily grade 1-2 liver enzyme elevations) were slightly higher in nivolumab-treated patients with liver metastases (10%) than in the overall pooled population (6%). Conclusions: After 3 years' minimum follow-up, nivolumab continued to demonstrate an OS benefit versus docetaxel in patients with advanced NSCLC. Similarly, nivolumab demonstrated an OS benefit versus docetaxel in patients with liver metastases, and remained well tolerated. Clinical trial registration: CheckMate 017: NCT01642004; CheckMate 057: NCT01673867.
RCT Entities:
Background: Long-term data with immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are limited. Two phase III trials demonstrated improved overall survival (OS) and a favorable safety profile with the anti-programmed death-1 antibody nivolumab versus docetaxel in patients with previously treated advanced squamous (CheckMate 017) and nonsquamous (CheckMate 057) NSCLC. We report results from ≥3 years' follow-up, including subgroup analyses of patients with liver metastases, who historically have poorer prognosis among patients with NSCLC. Patients and methods: Patients were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks) until progression or discontinuation. The primary end point of each study was OS. Patients with baseline liver metastases were pooled across studies by treatment for subgroup analyses. Results: After 40.3 months' minimum follow-up in CheckMate 017 and 057, nivolumab continued to show an OS benefit versus docetaxel: estimated 3-year OS rates were 17% [95% confidence interval (CI), 14% to 21%] versus 8% (95% CI, 6% to 11%) in the pooled population with squamous or nonsquamous NSCLC. Nivolumab was generally well tolerated, with no new safety concerns identified. Of 854 randomized patients across both studies, 193 had baseline liver metastases. Nivolumab resulted in improved OS compared with docetaxel in patients with liver metastases (hazard ratio, 0.68; 95% CI, 0.50-0.91), consistent with findings from the overall pooled study population (hazard ratio, 0.70; 95% CI, 0.61-0.81). Rates of treatment-related hepatic adverse events (primarily grade 1-2 liver enzyme elevations) were slightly higher in nivolumab-treated patients with liver metastases (10%) than in the overall pooled population (6%). Conclusions: After 3 years' minimum follow-up, nivolumab continued to demonstrate an OS benefit versus docetaxel in patients with advanced NSCLC. Similarly, nivolumab demonstrated an OS benefit versus docetaxel in patients with liver metastases, and remained well tolerated. Clinical trial registration: CheckMate 017: NCT01642004; CheckMate 057: NCT01673867.
Authors: Elizabeth J Cathcart-Rake; Lindsey R Sangaralingham; Henry J Henk; Nilay D Shah; Irbaz Bin Riaz; Aaron S Mansfield Journal: Clin Lung Cancer Date: 2020-04-13 Impact factor: 4.785
Authors: M P Petrova; I S Donev; M A Radanova; M I Eneva; E G Dimitrova; G N Valchev; V T Minchev; M S Taushanova; M V Boneva; T S Karanikolova; R B Gencheva; G A Zhbantov; A I Ivanova; C V Timcheva; B P Pavlov; V G Megdanova; B S Robev; N V Conev Journal: Clin Exp Immunol Date: 2020-08-26 Impact factor: 4.330
Authors: Daniel J Rubins; Xiangjun Meng; Paul McQuade; Michael Klimas; Krista Getty; Shu-An Lin; Brett M Connolly; Stacey S O'Malley; Hyking Haley; Mona Purcell; Liza Gantert; Marie Holahan; Joel Lindgren; Pär Eklund; Caroline Ekblad; Fredrik Y Frejd; Eric D Hostetler; Dinko E González Trotter; Jeffrey L Evelhoch Journal: Mol Imaging Biol Date: 2020-10-23 Impact factor: 3.488