Effect of early adverse events resulting in ado-trastuzumab emtansine dose adjustments on survival outcomes of HER2+ advanced breast cancer patients.

PURPOSE: Ado-trastuzumab emtansine (T-DM1) treatment in HER2+ advanced breast cancer patients is generally well tolerated, but when adverse events occur dose adjustments may be required. This study evaluated the impact of early adverse events requiring T-DM1 dose interruptions or reductions on overall survival (OS) and progression-free survival (PFS) in HER2+ advanced metastatic breast cancer patients in the clinical trials EMILIA and TH3RESA. PATIENTS AND METHODS: The study included 893 participants initiated on T-DM1 treatment. A landmark approach set at 4 months was used to evaluate the association between early adverse events requiring T-DM1 dose interruptions or reductions and OS/PFS. Cox proportional hazard analysis modeled the association between events requiring T-DM1 dose interruptions or reductions and OS/PFS. Associations were reported as hazard ratios with 95% confidence intervals. RESULTS: Adverse events requiring T-DM1 dose interruptions or reductions within the first 4 months of treatment were not significantly associated with OS (hazard ratio (HR) [95% CI]: dose interrupted = 1.15 [0.85-1.55]; dose reduced = 0.75 [0.49-1.14]; P = 0.214) nor PFS (hazard ratio (HR) [95% CI]: dose interrupted = 1.13 [0.87-1.48]; dose reduced = 0.90 [0.62-1.31]; P = 0.534). CONCLUSION: The occurrence of early adverse events requiring T-DM1 dose interruptions or reductions do not appear to be associated with altered long-term OS or PFS within a pooled analysis of data from EMILIA and TH3RESA.

Visualizing Ferroelectric Uniformity of Hf1-xZrxO2 Films Using X-ray Mapping.

Hf1-xZrxO2 (HZO) is a complementary metal-oxide-semiconductor (CMOS)-compatible ferroelectric (FE) material with considerable potential for negative capacitance field-effect transistors, ferroelectric memory, and capacitors. At present, however, the deployment of HZO in CMOS integrated circuit (IC) technologies has stalled due to issues related to FE uniformity. Spatially mapping the FE distribution is one approach to facilitating the optimization of HZO thin films. This paper presents a novel technique based on synchrotron X-ray nanobeam absorption spectroscopy capable of mapping the three main phases of HZO (i.e., orthorhombic (O), tetragonal (T), and monoclinic (M)). The practical value of the proposed methodology when implemented in conjunction with kinetic-nucleation modeling is demonstrated by our development of a T → O annealing (TOA) process to optimize HZO films. This process produces an HZO film with the largest polarization values (Ps = 64.5 µC cm-2; Pr = 35.17 µC cm-2) so far, which can be attributed to M-phase suppression followed by low-temperature annealing for the induction of a T → O phase transition.