Sixty-nine patients between the ages of 18 and 80 with invasive aspergillosis were enrolled in an open-label, noncomparative study to evaluate the safety, tolerability, and efficacy of CANCIDAS. Enrolled patients had previously been refractory to or intolerant of other antifungal therapy(ies). Refractory patients were classified as those who had disease progression or failed to improve despite therapy for at least 7 days with amphotericin B, lipid formulations of amphotericin B, itraconazole, or an investigational azole with reported activity against Aspergillus. Intolerance to previous therapy was defined as a doubling of creatinine (or creatinine ≥2.5 mg/dL while on therapy), other acute reactions, or infusion-related toxicity. To be included in the study, patients with pulmonary disease must have had definite (positive tissue histopathology or positive culture from tissue obtained by an invasive procedure) or probable (positive radiographic or computed tomography evidence with supporting culture from bronchoalveolar lavage or sputum, galactomannan enzyme-linked immunosorbent assay, and/or polymerase chain reaction) invasive aspergillosis. Patients with extrapulmonary disease had to have definite invasive aspergillosis. Patients were administered a single 70-mg loading dose of CANCIDAS and subsequently dosed with 50 mg daily. The mean duration of therapy was 33.7 days, with a range of 1 to 162 days.

An independent expert panel evaluated patient data, including diagnosis of invasive aspergillosis, response and tolerability to previous antifungal therapy, treatment course on CANCIDAS, and clinical outcome.

A favorable response was defined as either complete resolution (complete response) or clinically meaningful improvement (partial response) of all signs and symptoms and attributable radiographic findings. Stable, nonprogressive disease was considered to be an unfavorable response.

Among the 69 patients enrolled in the study, 63 met entry diagnostic criteria and had outcome data; and of these, 52 patients received treatment for greater than 7 days. Fifty-three (84%) were refractory to previous antifungal therapy and 10 (16%) were intolerant. Forty-five patients had pulmonary disease and 18 had extrapulmonary disease. Underlying conditions were hematologic malignancy (N=24), allogeneic bone marrow transplant or stem cell transplant (N=18), organ transplant (N=8), solid tumor (N=3), or other conditions (N=10). All patients in the study received concomitant therapies for their other underlying conditions. Eighteen patients received tacrolimus and CANCIDAS concomitantly, of whom 8 also received mycophenolate mofetil.

Overall, the expert panel determined that 41% (26/63) of patients receiving at least one dose of CANCIDAS had a favorable response. For those patients who received greater than 7 days of therapy with CANCIDAS, 50% (26/52) had a favorable response. The favorable response rates for patients who were either refractory to or intolerant of previous therapies were 36% (19/53) and 70% (7/10), respectively. The response rates among patients with pulmonary disease and extrapulmonary disease were 47% (21/45) and 28% (5/18), respectively. Among patients with extrapulmonary disease, 2 of 8 patients who also had definite, probable, or possible CNS involvement had a favorable response. Two of these 8 patients had progression of disease and manifested CNS involvement while on therapy.

CANCIDAS is effective for the treatment of invasive aspergillosis in patients who are refractory to or intolerant of itraconazole, amphotericin B, and/or lipid formulations of amphotericin B. However, the efficacy of CANCIDAS for initial treatment of invasive aspergillosis has not been evaluated in comparator-controlled clinical studies.