A randomized, double-blind, phase III, non-inferiority clinical trial comparing the efficacy and safety of TA4415V (a proposed Trastuzumab biosimilar) and Herceptin (Trastuzumab reference product) in HER2-positive early-stage breast Cancer patients.

BACKGROUND: This study compared efficacy and safety of TA4415V, a trastuzumab biosimilar, with reference trastuzumab in patients with human epidermal growth factor receptor 2-positive (HER2-positive) early-stage breast cancer treated in the neoadjuvant setting in Iran. METHODS: Patients were randomly assigned to receive neoadjuvant TA4415V or reference trastuzumab concurrently with docetaxel (TH phase) for 4 cycles after treatment with 4 cycles of doxorubicin and cyclophosphamide (AC phase). Chemotherapy was followed by surgery. The primary endpoint was the comparison of pathologic complete response (pCR) rate in the per-protocol population. Secondary endpoints included comparisons of overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity. RESULTS: Ninety-two participants were analyzed in the per-protocol population (TA4415V, n = 48; reference trastuzumab, n = 44). The pCR rates were 37.50% and 34.09% with TA4415V and reference drug, respectively. The 95% CI of the estimated treatment outcome difference (- 0·03 [95% CI - 0.23 to 0.16]) was within the non-inferiority margin. No statistically significant difference was observed between the groups for other efficacy variables in the ITT population: ORR (89.13% vs. 83.33%; p = 0.72) and BCS (20.37% vs. 12.96%; p = 0.42) in the TA4415V and reference drug group, respectively. At least one grade 3 or 4 adverse events occurred in 27 (50%) patients in the TA4415V group versus 29 (53.70%) in the reference trastuzumab group (p = 0.70). The decrease in left ventricular ejection fraction (LVEF), as an adverse event of special interest (AESI) for trastuzumab, was compared between treatment groups in TH phase. Results demonstrated an LVEF decrease in 7 (12.96%) and 9 (16.67%) patients in TA4415V and reference trastuzumab groups, respectively (p = 0.59). Anti-drug antibodies (ADA) were not detected in any samples of groups. CONCLUSIONS: Non-inferiority for efficacy was demonstrated between TA4415V and Herceptin based on the ratio of pCR rates in HER2-positive early breast cancer patients. In addition, ORR and BCS, as secondary endpoints, were not significantly different. Safety profile and immunogenicity were also comparable between the two groups.

Oropharyngeal Candida Colonization in Patients with Acute Myeloid Leukemia.

OBJECTIVES: Oral candidiasis has increased in recent years because of the increasing number of high-risk populations. The prevalence of Candida species is different worldwide because of the difference between population characteristics, sampling protocols, and geographic regions. Therefore, determining the more prevalent Candida species in different geographic regions seems essential. This study aimed to determine the more prevalent Candida species in acute myeloid leukemia (AML) patients in comparison with healthy individuals in Iran in 2016. MATERIALS AND METHODS: Fifty-one patients with AML and 62 healthy controls participated in this cross-sectional study. Samples were collected using a swab rubbed softly on the dorsal surface of the tongue and the oropharynx. The samples were cultured on CHROMagar Candida for 2 to 4 days. For differentiation between albicans and non-albicans species, positive samples were linearly inoculated on Corn Meal Agar with Tween-80. Candida species were identified using a microscope. Data were analyzed using chi-square and Fisher's exact tests. RESULTS: Candida colonization was more frequent in AML patients (41.2%) in comparison with healthy participants (38.7%). Candida glabrata (C. glabrata; 27.5%) and Candida albicans (C. albicans; 32.3%) were the most common isolated species in the AML patients and the controls, respectively. There was a significant decrease in the frequency of C. albicans (P=0.022) and a significant increase in the frequency of C. glabrata (P=0.002) in the AML patients in comparison with the controls. CONCLUSION: AML patients are more susceptible to candidiasis. C. glabrata is the dominant Candida species in AML patients.