Sapporo National Hospital

This study aimed to examine the effects of concomitant use of proton-pump inhibitors (PPIs) on the survival outcomes in patients with endocrine-sensitive chemotherapy-naïve advanced breast cancer (BC) treated with palbociclib or abemaciclib. This multicenter, retrospective study was conducted at five hospitals in Japan. Data were collected from consecutive patients treated with palbociclib or abemaciclib in combination with endocrine therapy as first-line treatment for endocrine-sensitive chemotherapy-naïve advanced BC between December 2017 and August 2022. Associations between concomitant PPI use and survival outcomes were analyzed. Among 202 patients, 38 (19%) were concomitant PPI users. In the palbociclib population (n = 123), concomitant PPI use was associated with a trend toward decreased progression-free survival (PFS) and a significant reduction in overall survival (OS; crude hazard ratio [HR], 1.67; 95% confidence interval [CI], 0.86–3.00 and crude HR, 3.51; 95% CI, 1.53–7.64, respectively). In multivariable analyses, consistent results were obtained (adjusted HR, 1.29; 95% CI, 0.66–2.53 and adjusted HR, 3.23; 95% CI, 1.28–7.67, respectively). In contrast, concomitant PPI use did not significantly affect either PFS or OS in the abemaciclib group (n = 79). Concomitant PPI use decreased the efficacy of palbociclib regardless of the formulation, with no such impact observed with abemaciclib.

Correction: Overall survival of palbociclib plus endocrine therapy in Japanese patients with HR+/HER2- advanced breast cancer in the first-or second-line setting: a multicenter observational study (P-BRIDGE study)

ObjectiveThis study aimed to evaluate cyclophosphamide contamination in community pharmacies, investigate patient-mediated transfer and indirect risks to the public, and examine the association between the use of hospital closed system transfer devices (CSTDs) and this contamination.MethodsWipe samples from patient counselling counters at 24 community pharmacies near 10 hospitals were analysed for cyclophosphamide contamination using liquid chromatography-mass spectrometry. A questionnaire survey was conducted to assess CSTD use and cleaning practices.ResultsContamination was detected in 5/24 pharmacies (20.8%; median level: 0.7ng/625cm2). The overall median across the 24 pharmacies was below the limit of quantification, which does not necessarily indicate absence of contamination. Moreover, four of the five pharmacies with contamination did not have cyclophosphamide in stock during the sampling period. Contamination was observed irrespective of hospital CSTD use or the pharmacy's handling of cyclophosphamide.ConclusionsCyclophosphamide contamination detection on patient counselling counters in community pharmacies may be a result of patient-mediated transfer. However, alternative sources within pharmacies, such as inventory, packaging, and local handling, cannot be ruled out. Contamination was detected in settings with and without hospital CSTD use, indicating that CSTDs address handling-related contamination but do not mitigate patient-mediated pathways.

34 participating institutions'.

We report a case of Erdheim-Chester disease (ECD) presenting with recurrent mass lesions that posed significant diagnostic challenges. The patient, a 66-year-old man, had multiple recurrent intracranial lesions with contrast enhancement and edema. Given his history of international travel and partial responsiveness to antibiotics, imported infectious diseases were initially suspected. However, infectious etiology was ruled out based on histopathological examination, leading to a diagnosis of ECD. This case was atypical for ECD due to the imaging findings and recurrent nature of the lesions. When granulomatous lesions with histiocytic infiltration are non-infectious, histiocytic disorders should be considered, and immunohistochemical staining is recommended.

Purpose:Seizure-related homolog protein 6 (SEZ6) is a novel target expressed in small cell lung cancer (SCLC). ABBV-011, a SEZ6-targeted antibody conjugated to calicheamicin, was evaluated in a phase I study (NCT03639194) in patients with relapsed/refractory SCLC. We report initial outcomes of ABBV-011 monotherapy.Patients and Methods:ABBV-011 was administered intravenously once every 3 weeks during dose escalation (0.3–2 mg/kg) and expansion. Patients with SEZ6-positive tumors (≥25% of tumor cells with ≥1+ staining intensity by IHC) were preselected for expansion. Safety, tolerability, antitumor activity, and pharmacokinetics were evaluated.Results:As of August 2022, 99 patients received ABBV-011 monotherapy [dose escalation, n = 36; Japanese dose evaluation, n = 3; dose expansion, n = 60 (1 mg/kg, n = 40)]; the median age was 63 years (range, 41–79 years). Also, 32%, 41%, and 26% of patients received 1, 2, and ≥3 prior therapies, respectively. The maximum tolerated dose was not reached through 2.0 mg/kg. The most common treatment-emergent adverse events were fatigue (50%), nausea (42%), and thrombocytopenia (41%). The most common hepatic treatment-emergent adverse events were increased aspartate aminotransferase (22%), increased γ-glutamyltransferase (21%), and hyperbilirubinemia (17%); two patients experienced veno-occlusive liver disease. The objective response rate was 19% (19/98). In the 1-mg/kg dose-expansion cohort (n = 40), the objective response rate was 25%; the median response duration was 4.2 months (95% confidence interval, 2.6–6.7); and the median progression-free survival was 3.5 months (95% confidence interval, 1.5–4.2).Conclusions:ABBV-011 1.0 mg/kg every 3 weeks monotherapy was well tolerated and demonstrated encouraging antitumor activity in heavily pretreated patients with relapsed/refractory SCLC. SEZ6 is a promising novel SCLC target and warrants further investigation.