Dimitrios P Kontoyiannis1, Dominik Selleslag2, Kathleen Mullane3, Oliver A Cornely4, William Hope5, Olivier Lortholary6, Rodney Croos-Dabrera7, Christopher Lademacher7, Marc Engelhardt8, Thomas F Patterson9. 1. Department of Infectious Diseases, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 2. AZ Sint Jan Brugge Oostende AV, Brugge, Belgium. 3. Department of Medicine/Section of Infectious Diseases, University of Chicago, Chicago, IL, USA. 4. Department I for Internal Medicine, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, Clinical Trials Centre, University of Cologne (ZKS Köln), Cologne, Germany. 5. University of Liverpool, Liverpool, UK. 6. Université Paris Descartes, Centre d'Infectiologie Necker Pasteur, Paris, France. 7. Astellas Pharma Global Development, Inc., Northbrook, IL, USA. 8. Basilea Pharmaceutica International Ltd, Basel, Switzerland. 9. Infectious Disease, UT Health San Antonio and the South Texas Veterans Health Care System, San Antonio, TX, USA.
Abstract
Background: Historically, baseline neutropenia and lack of neutrophil recovery have been associated with poor outcomes in invasive aspergillosis (IA). It is unclear how treatment with the new Aspergillus-active triazoles isavuconazole and voriconazole affects outcomes in neutropenic patients with IA. Methods: A post hoc analysis of the Phase 3 SECURE trial assessed patients with neutropenia (neutrophil count <0.5 × 109/L for >10 days at baseline) with IA (proven/probable) who had received either isavuconazole or voriconazole. The primary endpoint was all-cause mortality (ACM) through day 42. ACM in patients with resolved versus unresolved neutropenia at day 7 and overall success at end of treatment (EOT) were also assessed. Results:One hundred and forty-two patients with neutropenia and IA were included (isavuconazole n = 78, voriconazole n = 64). ACM through day 42 (primary endpoint), day 7 and EOT were higher for patients with unresolved versus resolved neutropenia at each timepoint (day 42, unresolved: 45.0% isavuconazole, 45.2% voriconazole; resolved: 5.0% isavuconazole, 5.9% voriconazole; day 7, unresolved: 31.0% isavuconazole, 29.8% voriconazole; resolved: 5.0% isavuconazole, 5.9% voriconazole; EOT, unresolved: 48.6% isavuconazole, 36.4% voriconazole; resolved: 5.0% isavuconazole, 14.3% voriconazole). ACM was significantly higher for isavuconazole-treated patients with unresolved versus resolved neutropenia (day 7, P = 0.031; day 42, P < 0.001; EOT, P < 0.001). In voriconazole-treated patients, ACM was significantly higher among patients with unresolved versus resolved neutropenia at day 42 (P = 0.002) and numerically higher at day 7 and EOT (P > 0.05 for both). Conclusions: Isavuconazole had comparable efficacy and safety to voriconazole in neutropenic patients with IA. Resolution of neutropenia was associated with improved outcomes.
RCT Entities:
Background: Historically, baseline neutropenia and lack of neutrophil recovery have been associated with poor outcomes in invasive aspergillosis (IA). It is unclear how treatment with the new Aspergillus-active triazolesisavuconazole and voriconazole affects outcomes in neutropenicpatients with IA. Methods: A post hoc analysis of the Phase 3 SECURE trial assessed patients with neutropenia (neutrophil count <0.5 × 109/L for >10 days at baseline) with IA (proven/probable) who had received either isavuconazole or voriconazole. The primary endpoint was all-cause mortality (ACM) through day 42. ACM in patients with resolved versus unresolved neutropenia at day 7 and overall success at end of treatment (EOT) were also assessed. Results: One hundred and forty-two patients with neutropenia and IA were included (isavuconazole n = 78, voriconazole n = 64). ACM through day 42 (primary endpoint), day 7 and EOT were higher for patients with unresolved versus resolved neutropenia at each timepoint (day 42, unresolved: 45.0% isavuconazole, 45.2% voriconazole; resolved: 5.0% isavuconazole, 5.9% voriconazole; day 7, unresolved: 31.0% isavuconazole, 29.8% voriconazole; resolved: 5.0% isavuconazole, 5.9% voriconazole; EOT, unresolved: 48.6% isavuconazole, 36.4% voriconazole; resolved: 5.0% isavuconazole, 14.3% voriconazole). ACM was significantly higher for isavuconazole-treated patients with unresolved versus resolved neutropenia (day 7, P = 0.031; day 42, P < 0.001; EOT, P < 0.001). In voriconazole-treated patients, ACM was significantly higher among patients with unresolved versus resolved neutropenia at day 42 (P = 0.002) and numerically higher at day 7 and EOT (P > 0.05 for both). Conclusions: Isavuconazole had comparable efficacy and safety to voriconazole in neutropenicpatients with IA. Resolution of neutropenia was associated with improved outcomes.
Authors: Romy Tober; Ulf Schnetzke; Maximilian Fleischmann; Olaposi Yomade; Karin Schrenk; Jakob Hammersen; Anita Glaser; Christian Thiede; Andreas Hochhaus; Sebastian Scholl Journal: J Cancer Res Clin Oncol Date: 2022-05-18 Impact factor: 4.553
Authors: Palash Samanta; Cornelius J Clancy; Rachel V Marini; Ryan M Rivosecchi; Erin K McCreary; Ryan K Shields; Bonnie A Falcione; Alex Viehman; Lauren Sacha; Eun Jeong Kwak; Fernanda P Silveira; Pablo G Sanchez; Matthew Morrell; Lloyd Clarke; M Hong Nguyen Journal: Clin Infect Dis Date: 2021-08-02 Impact factor: 9.079