Quality of life in women with early-stage and metastatic hormone receptor-positive, HER2-negative breast cancer receiving endocrine therapy.

INTRODUCTION: Early discontinuation of endocrine therapy (ET) is higher among patients with early breast cancer (EBC) compared to patients with metastatic hormone receptor-positive (HR+) breast cancer (MBC). In our clinical experience the reasons for this may include a significant burden of ET side effects impacting quality of life (QOL) in patients with EBC.  We hypothesized that QOL is lower in patients with HR + EBC compared to patients with HR + MBC on ET. METHODS: We conducted a cross-sectional observational study to assess QOL utilizing FACT-ES & EORTC QLQ C30 tools among patients with EBC and MBC receiving ET across 5 Irish hospitals. RESULTS: A total of 417 patients were enrolled-EBC (79% n = 331) and MBC 21% (n = 86). Using the FACT-ES, we found no difference in overall QOL by stage (139.2 vs 141, P  = .33). Patients with HR + MBC had a lower symptom burden from ET compared to HR + EBC (61.4 vs 54, P < .01). In adjusted multivariate linear regression models, there was no difference in QOL for patients with EBC and MBC receiving ET. CONCLUSIONS: There was no significant difference in overall QOL for patients with EBC and MBC. However, patients with EBC experienced more endocrine symptoms. In adjusted multivariate linear regression models, the stage did not predict QOL. Our results suggest that endocrine symptoms are significant contributors to impaired QOL for patients with EBC but the role of other determinants of QOL (eg, stage) is less clear. Future work could include the development of stage-specific QOL tools and utilization of electronic patient-reported outcomes (ePROs) to identify and manage emergent toxicities.

Cost and public reimbursement of cancer medicines in the UK and the Republic of Ireland.

INTRODUCTION/AIMS: There are disparities in the availability of systemic anticancer therapies (SACTs) globally. We set out to investigate the cost and reimbursement of SACTs in the United Kingdom (UK) and the Republic of Ireland (ROI) in conjunction with efficacy and licensing authority decisions in the United States (US) and the European Union (EU). METHODS: We sought data pertaining to licensing in the EU, reimbursement in ROI/UK and cost/efficacy of SACTs licensed by the Food and Drug Administration (FDA) between January 2015 and May 2021. Independent samples t tests, chi-square test and Pearson's correlation were used for statistical analysis. RESULTS: We identified that the majority of FDA-approved regimens are licensed by the European Medicines Agency (EMA) (n = 91, 67.9%). However, only a minority of these are currently reimbursed in the UK (n = 60, 45%) or the ROI (n = 28, 21%) as of the 1st of May 2021. In addition, only a minority of regimens have demonstrated a statistically significant OS benefit (n = 54, 40%). There was no association between cost of regimens and either the presence (t = 0.846, p = 0.40) or duration of OS benefit (t = - 0.84, p = 0.64). CONCLUSIONS: Our study highlights that many licensed systemic anticancer treatments are not currently reimbursed in ROI/UK. The high cost of these medicines is independent of the presence of an OS benefit. Collaboration between regulatory agencies, governments and industry partners is needed to ensure health expenditure is directed towards the most effective treatments.

A pilot project investigating the use of ONCOpatient®-An electronic patient-reported outcomes app for oncology patients.

Purpose: To investigate the feasibility of implementing a remote patient monitoring system using an electronic patient-reported outcomes (ePROs) platform in a tertiary cancer center in the Republic of Ireland. Methods: Patients receiving oral chemotherapy and oncology clinicians were invited to participate in the study. Patients were asked to submit weekly symptom questionnaires through an ePRO mobile phone application (app)-ONCOpatient®. Clinical staff were invited to use the ONCOpatient® clinician interface. After 8 weeks all participants submitted evaluation questionnaires. Results: Thirteen patients and five staff were enrolled in the study. The majority of patients were female (85%) with a median age of 48 years (range 22-73). Most (92%) were enrolled over telephone requiring on average 16 minutes. Compliance with the weekly assessments was 91%. Alerts were triggered by 40% of patients who then required phone calls to aid with symptom management. At the end of study, 87% of patients reported they would use the app frequently, 75% reported that the platform met their expectations, and 25% that it exceeded their expectations. Similarly, 100% of staff reported they would use the app frequently, 60% reported that it met their expectations, and 40% that it exceeded their expectations. Conclusions: Our pilot study showed that it is feasible to implement ePRO platforms in the Irish clinical setting. Small sample bias was recognized as a limitation, and we plan to confirm our findings on a larger cohort of patients. In the next phase we will integrate wearables including remote blood pressure monitoring.

Role of p21-activated kinase in cell polarity and directional mesendoderm migration in the Xenopus gastrula.

The p21 activated kinases (Paks) are prominently involved in the regulation of cell motility. Using a kinase-dead mutant of xPak1, we show that during Xenopus gastrulation, the kinase activity of Pak1 is required upstream of Cdc42 for the establishment of cell polarity in the migrating mesendoderm. Overactivation of Pak1 function by the expression of constitutively active xPak1 compromises the maintenance of cell polarity, by indirectly inhibiting RhoA function. Inhibition of cell polarization does not affect the migration of single mesendoderm cells. However, Pak1 inhibition interferes with the guidance of mesendoderm migration by directional cues residing in the extracellular matrix of the blastocoel roof, and with mesendoderm translocation in the embryo.