1149. Baseline Chest CT Findings in Patients with Pulmonary Mold Infections: A Post-Hoc Analysis from the Phase 3 SECURE Study that Compared Isavuconazole to Voriconazole for the Primary Treatment of Invasive Mold Disease
Authors: Hamed Kamal , Engelhardt Marc , Saulay Mikael , Kovanda Laura 
Published: January 2021

Abstract

Background
SECURE was a global, double-blind, Phase 3 study that randomized 527 patients 1:1 to isavuconazole (ISAV) or voriconazole (VORI) for the primary treatment of invasive mold disease (IMD) caused by Aspergillus or other filamentous fungi. Patients were classified as having proven/probable IMD (PP-IMD) or possible IMD (PS-IMD) according to EORTC/MSG 2008 criteria, and the majority (n=412) had pulmonary disease only. This post-hoc analysis describes baseline CT findings in these patients and explores the association between these findings and treatment outcomes.

Methods
A blinded, independent review committee assessed the certainty of diagnosis (PP-IMD vs PS-IMD), location of disease (pulmonary only, pulmonary plus other organ, non-pulmonary only), and both overall and clinical responses at end-of-treatment. Radiology assessments were done by central blinded radiologists who characterized pulmonary lesions as follows: well-defined nodule(s) with or without halo sign, wedge-shaped infiltrate, cavity, air crescent sign, or non-specific focal infiltrate.

Results
Of the 412 patients with pulmonary disease only, 223 (54%) had PP-IMD and 189 (46%) had PS-IMD. Well-defined nodule(s) was the predominant radiological finding at baseline in patients with PP-IMD or PS-IMD (PP-IMD 55%, PS-IMD 63%), followed by non-specific focal infiltrate (PP-IMD 43%, PS-IMD 41%), wedge-shaped infiltrate (PP-IMD 24%, PS-IMD 30%), and halo (PP-IMD 25%, PS-IMD 28%). A small proportion of patients had a cavity (PP-IMD 12%, PS-IMD 9%) or air crescent sign (PP-IMD 2%, PS-IMD 4%).
Patients with air crescent sign had low all-cause mortality through Days 42 and 84, and high overall and clinical response rates at end-of treatment (PP-IMD: 0, 0, 75%, 100% and PS-IMD: 0, 13%, 75%, 88%, respectively). There was no other clear association between baseline CT findings and either outcomes of all-cause mortality or overall and clinical responses.
Figure. Chest CT findings at baseline in patients with PP-IMD or PS-IMD (pulmonary only)

Conclusion
In patients with pulmonary IMD, the predominant radiological finding at baseline was well-defined nodule(s) in both PP-IMD and PS-IMD. Air crescent sign was infrequent, but was associated with lower all-cause mortality and higher overall and clinical responses. Otherwise, baseline CT findings did not appear to predict treatment outcomes in this Phase 3 study.

Disclosures
Kamal Hamed, n/a, Basilea Pharmaceutica International Ltd. (Employee) Marc Engelhardt, n/a, Basilea Pharmaceutica International Ltd. (Board Member, Consultant, Employee, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support, Shareholder, Speaker’s Bureau, Independent Contractor, Other Financial or Material Support)Basilea Pharmaceutica International Ltd. (Employee) Mikael Saulay, n/a, Basilea Pharmaceutica International Ltd. (Employee) Laura Kovanda, n/a, Astellas Pharma Inc (Employee)