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

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.