Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial.

BACKGROUND: HER2 mutations are targetable alterations in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). In the SUMMIT basket study, patients with HER2-mutant MBC received neratinib monotherapy, neratinib + fulvestrant, or neratinib + fulvestrant + trastuzumab (N + F + T). We report results from 71 patients with HR+, HER2-mutant MBC, including 21 (seven in each arm) from a randomized substudy of fulvestrant versus fulvestrant + trastuzumab (F + T) versus N + F + T. PATIENTS AND METHODS: Patients with HR+ HER2-negative MBC with activating HER2 mutation(s) and prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy received N + F + T (oral neratinib 240 mg/day with loperamide prophylaxis, intramuscular fulvestrant 500 mg on days 1, 15, and 29 of cycle 1 then q4w, intravenous trastuzumab 8 mg/kg then 6 mg/kg q3w) or F + T or fulvestrant alone. Those whose disease progressed on F + T or fulvestrant could cross-over to N + F + T. Efficacy endpoints included investigator-assessed objective response rate (ORR), clinical benefit rate (RECIST v1.1), duration of response, and progression-free survival (PFS). Plasma and/or formalin-fixed paraffin-embedded tissue samples were collected at baseline; plasma was collected during and at end of treatment. Extracted DNA was analyzed by next-generation sequencing. RESULTS: ORR for 57 N + F + T-treated patients was 39% [95% confidence interval (CI) 26% to 52%); median PFS was 8.3 months (95% CI 6.0-15.1 months). No responses occurred in fulvestrant- or F + T-treated patients; responses in patients crossing over to N + F + T supported the requirement for neratinib in the triplet. Responses were observed in patients with ductal and lobular histology, 1 or ≥1 HER2 mutations, and co-occurring HER3 mutations. Longitudinal circulating tumor DNA sequencing revealed acquisition of additional HER2 alterations, and mutations in genes including PIK3CA, enabling further precision targeting and possible re-response. CONCLUSIONS: The benefit of N + F + T for HR+ HER2-mutant MBC after progression on CDK4/6is is clinically meaningful and, based on this study, N + F + T has been included in the National Comprehensive Cancer Network treatment guidelines. SUMMIT has improved our understanding of the translational implications of targeting HER2 mutations with neratinib-based therapy.

Achromobacter xylosoxidans bacteremia: a 10-year analysis of 54 cases.

Fifty-four cases of Achromobacter xylosoxidans bacteremia diagnosed over a 10-year period in patients from 2 months to 87 years of age were reviewed. Fifty-two episodes were nosocomial. The most frequent underlying condition was neoplasm (solid or hematological). The source of infection was a contaminated intravenous catheter in 35 patients (60%) and pneumonia in 6 patients. Eight (15%) patients died. The only risk factors significantly associated with mortality were age over 65 years and neutropenia. The results of in vitro susceptibility studies of the isolates showed that antibiotic therapy with antipseudomonal penicillins or carbapenems would be a reasonable choice. An epidemiological study conducted in the hemodialysis unit showed Achromobacter xylosoxidans in tap water and on the hands of two healthcare workers but not in the hemodialysis systems. Patients were probably contaminated when healthcare workers manipulated the intravenous catheters without wearing gloves.

[Radioprotective effect of ascorbic acid on oral structures in patients with cancer of the head and neck]. / Efecto radioprotector del acido ascorbico sobre estructuras orales en pacientes con cancer de cabeza y cuello.

It is considered the radioprotective effect of ascorbic acid in patients with head and neck cancer. It is observed a reduction of yatrogenic effects over oral structures secondary to radiotherapy. It is recommended the oral administration of ascorbic acid in this type of patients.

[Oral manifestations in tuberous sclerosis. Report of 3 cases]. / Manifestaciones orales en esclerosis tuberosa. Presentación de tres casos.

We present three cases of Tuberous Sclerosis, studying its oral manifestations and suggesting that dental pits are clinical markers of diagnostic interest in the paucisymptomatic forms of the syndrome.

Cellular immunodeficiency with immunoglobulins: treatment with a thymus implant in millipore diffusion chambers.

A 14 month old male affected by cellular immunodeficiency with immunoglobulins underwent implantation of a thymus enclosed in Millipore diffusion chambers. Five days after the implant the percentage of T lymphocytes forming spontaneous rosettes reached normal levels. One month later responsiveness to PHA was demonstrated in the patient's lymphocytes and IgG and IgM serum levels showed a marked increase. Positive skin tests were elicited 6 month's post-implant. An inguinal lymph node biopsy showed developing primary follicles and germinal centers. The patient's condition improved significantly. One year after the implant the patient died from irreversible neurological deterioration. It is suggested that partial immunological reconstitution was achieved by thymic humoral factors.