A pooled analysis of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer with brain metastases.

BACKGROUND: This exploratory pooled analysis investigated the efficacy and safety of trastuzumab deruxtecan (T-DXd) versus comparator treatment in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) with brain metastases (BMs) at baseline, categorized according to previous local treatment. PATIENTS AND METHODS: T-DXd data were pooled from DESTINY-Breast01/-02/-03. Comparator data, from patients receiving physician's choice therapy and trastuzumab emtansine, were pooled from DESTINY-Breast02 and -03, respectively. Baseline BM status was assessed according to US Food and Drug Administration criteria. The endpoints included intracranial objective response rate (ORR; complete or partial response in the brain) per blinded independent central review (BICR) by RECIST version 1.1, time to intracranial response, intracranial duration of response (DoR), central nervous system progression-free survival (CNS-PFS) by BICR, overall survival (OS), and safety. RESULTS: A total of 148 patients who received T-DXd and 83 patients who received comparator treatment had BMs at baseline. In those treated with T-DXd, the intracranial ORR of patients with treated/stable and untreated/active BMs was 45.2% and 45.5%, respectively. The median (range) time to intracranial response was 2.8 months (1.1-13.9 months) and 1.5 months (1.2-13.7 months) in patients with treated/stable and untreated/active BMs, respectively. For those with treated/stable BMs, the median intracranial DoR was 12.3 [95% confidence interval (CI) 9.1-17.9] months, and for those with untreated/active BMs, it was 17.5 months (95% CI 13.6-31.6 months). The median CNS-PFS and OS were 12.3 months (95% CI 11.1-13.8 months) and not reached (95% CI 22.1 months-not estimable) in those with treated/stable BMs, and 18.5 months (95% CI 13.6-23.3 months) and 30.2 months (95% CI 21.3 months-not estimable) in those with untreated/active BMs, respectively. Drug-related treatment-emergent adverse events grade ≥3 were experienced by 43.2% of patients with BMs and 46.4% without BMs with T-DXd. CONCLUSIONS: T-DXd demonstrated meaningful intracranial efficacy and clinical benefit in OS, with an acceptable and manageable safety profile in patients with HER2-positive mBC with treated/stable and untreated/active BMs.

Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer patients with brain metastases from the randomized DESTINY-Breast03 trial.

BACKGROUND: DESTINY-Breast03 is a randomized, multicenter, open-label, phase III study of trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab and a taxane. A statistically significant improvement in progression-free survival (PFS) versus T-DM1 was reported in the primary analysis. Here, we report exploratory efficacy data in patients with and without brain metastases (BMs) at baseline. PATIENTS AND METHODS: Patients were randomly assigned 1 : 1 to receive T-DXd 5.4 mg/kg or T-DM1 3.6 mg/kg. Patients with clinically inactive/asymptomatic BMs were eligible. Lesions were measured as per modified RECIST, version 1.1. Outcomes included PFS by blinded independent central review (BICR), objective response rate (ORR), and intracranial ORR as per BICR. RESULTS: As of 21 May 2021, 43/261 patients randomized to T-DXd and 39/263 patients randomized to T-DM1 had BMs at baseline, as per investigator assessment. Among patients with baseline BMs, 20/43 in the T-DXd arm and 19/39 in the T-DM1 arm had not received prior local BM treatment. For patients with BMs, median PFS was 15.0 months [95% confidence interval (CI) 12.5-22.2 months] for T-DXd versus 3.0 months (95% CI 2.8-5.8 months) for T-DM1; hazard ratio (HR) 0.25 (95% CI 0.13-0.45). For patients without BMs, median PFS was not reached (95% CI 22.4 months-not estimable) for T-DXd versus 7.1 months (95% CI 5.6-9.7 months) for T-DM1; HR 0.30 (95% CI 0.22-0.40). Confirmed systemic ORR was 67.4% for T-DXd versus 20.5% for T-DM1 and 82.1% for T-DXd versus 36.6% for T-DM1 for patients with and without BMs, respectively. Intracranial ORR was 65.7% with T-DXd versus 34.3% with T-DM1. CONCLUSIONS: Patients with HER2-positive mBC whose disease progressed after trastuzumab and a taxane achieved a substantial benefit from treatment with T-DXd compared with T-DM1, including those with baseline BMs.

An efficient method for quantifying the multichannel EEG spatial-temporal complexity.

The complexity index (delta) quantifies the intrinsic dimensionality of the global complexity of a point set, and was shown to be able to characterize electroencephalogram spatial-temporal features. The complexity index is conceptually comprehensible and easily implemented, yet, it is time consuming. In this paper, we present an efficient computational method based on the projection of the high-dimensional state-space points onto a one-dimensional axis. The computational time decreases by at least 50%, without affecting the measure accuracy.

Characterization of tryptic peptides from porcine haptoglobin light chain and an amino acid sequence.

The tryptic peptides derived from porcine haptoglobin light chains have been separated and characterized by composition, chromatography, electrophoretic mobility, and partial sequencing. Depending on homology with the corresponding human polypeptide, the amino acid sequence of the chain is proposed. Twenty differences from the human chain are indicated in the total of 84 residues.