Treatment outcomes in patients with proven/probable vs possible invasive mould disease in a phase III trial comparing isavuconazole vs voriconazole

Abstract

Treatment outcomes in patients with proven/probable vs possible invasive mould disease (IMD; 2008 European Organisation for Research and Treatment of Cancer/Mycoses Study Group [EORTC/MSG] criteria) needed further assessment. The Phase III SECURE trial compared isavuconazole vs voriconazole for treatment of IMD. This post hoc analysis assessed all-cause mortality (ACM) through day 42 (primary endpoint) and day 84, overall and clinical success at end of treatment (EOT), and drug-related treatment-emergent adverse events (TEAEs) in subgroups with proven/probable or possible IMD. Of 516 randomised patients, 304 (58.9%) had proven/probable IMD and 164 (31.8%) had possible IMD as per EORTC/MSG criteria; 48 did not have IMD. Across treatment groups, day 42 and day 84 ACM were numerically lower for possible vs proven/probable IMD (day 42: 17.1% vs 21.1%; P = 0.3, day 84: 26.2% vs 32.6%; P = 0.15). Overall and clinical success at EOT were significantly higher for possible IMD compared with proven/probable IMD (48.2% vs 36.2%; P = 0.01, 75.0% vs 63.1%; P = 0.01 respectively). Fewer drug-related TEAEs were reported with isavuconazole compared with voriconazole in patients with either proven/probable or possible IMD. Compared with patients with proven/probable IMD, those with possible IMD demonstrated higher overall and clinical success rates, supporting early initiation of antifungal treatment.

Clinical experience with isavuconazole in healthy volunteers and patients with invasive aspergillosis in China, and the results from an exposure–response analysis

“…While voriconazole has demonstrated superiority, compared with amphotericin B deoxycholate for the initial treatment of IA, 20 isavuconazole has been shown to be non‐inferior to voriconazole for the primary treatment of suspected invasive mould disease, as demonstrated in the global Phase III SECURE study (NCT00412893) 21 . Additionally, fewer treatment‐related treatment‐emergent adverse events (TEAEs) were observed in patients who received isavuconazole compared with patients who received voriconazole in a post hoc analysis of the SECURE study in patients with proven/probable invasive mould disease, and in a retrospective study of the medical records of patients with chronic pulmonary aspergillosis 22,23 …”

“…21 Additionally, fewer treatment-related treatment-emergent adverse events (TEAEs) were observed in patients who received isavuconazole compared with patients who received voriconazole in a post hoc analysis of the SECURE study in patients with proven/probable invasive mould disease, and in a retrospective study of the medical records of patients with chronic pulmonary aspergillosis. 22,23 However, despite guideline recommendations, even when diagnosed and treated appropriately, IA remains a disease associated with poor survival and an increased length of hospital stay in China. 24 Thus, with the increasing size of the 'at-risk' population, and few effective treatment options, there remains an unmet medical need for better treatments for invasive fungal disease (IFD) in China.…”

Treatment of invasive fungal diseases in cancer patients—Revised 2019 Recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)

“…According to the results of this large study, isavuconazole was non‐inferior to voriconazole for the primary treatment of suspected invasive mold disease. In a post hoc analysis, overall and clinical success at EOT was significantly higher for possible IFD compared with proven/probable IFD 34 . This trial offers strong evidence that isavuconazole is an appropriate alternative to voriconazole for first‐line treatment of invasive aspergillosis and other mold disease (AI).…”

Short course of voriconazole therapy as a risk factor for relapse of invasive pulmonary aspergillosis

“…Invasive pulmonary aspergillosis (IPA) is an infectious disease with a mortality rate of about 30% 1 , 2 . Immunocompromised patients with prolonged neutropenia or taking corticosteroids, and those who received allogeneic hematopoietic stem cell transplantation (HCT) or solid-organ transplantation, and with severe influenza are at high risk of IPA 3 , 4 .…”

“…With respect to the radiological findings, the most common pattern of lung lesions was ground-glass opacity with a halo (78.6% vs. 80.6%; P = 1.000), followed by a nodule or mass (78.6% vs. 79.2%; P = 1.000) regardless of the relapse. The initial number of involved lobes was not significantly different between the two groups (median [IQR], 3 [2][3][4][5] vs. 3 [2][3][4][5]; P = 0.975). Radiological response (28.6% vs. 61.8%; P = 0.023) was significantly higher in the non-relapse group than in the relapse group, but there was no difference in the rate of complete response (CR) (21.4% vs. 14.7%; P = 0.687).…”