Effectiveness,safety and quality of life of trifluridine/tipiracil in pretreated patients with metastatic colorectal cancer: Real-world data from the noninterventional TACTIC study in Germany

The prospective, multicenter, noninterventional TACTIC study assessed effectiveness and safety of trifluridine/tipiracil (FTD/TPI) in patients with metastatic colorectal cancer (mCRC) in a real-world setting in Germany, thus evaluating the external validity of the findings from the pivotal RECOURSE trial. Primary endpoint was overall survival (OS). Secondary objectives included progression-free survival (PFS), safety, and quality of life (QoL). Subgroups comprised patients with good (<3 metastatic sites at inclusion, ≥18 months from diagnosis of first metastasis to inclusion) or poor (remaining patients) prognostic characteristics (GPC/PPC). GPC without liver metastases was considered best prognostic characteristics (BPC). In total, 307 eligible patients (pretreated or not suitable for other available therapies) were treated with FTD/TPI. Overall, median [95%-CI] OS was 7.4 months [6.4-8.6], median PFS was 2.9 months [2.8-3.3]. In BPC (n = 65) and GPC (n = 176) compared to PPC (n = 124) subgroup, median OS (13.3 [9.1-17.6] vs 8.9 [7.6-9.8] vs 5.1 [4.4-7.0] months) and median PFS (4.0 [3.3-5.3] vs 3.4 [3.0-3.7] vs 2.6 [2.4-2.8] months) were longer. Patient-reported QoL, assessed by validated questionnaires (EQ-5D-5L, PRO-CTCAE), was stable throughout FTD/TPI treatment. Predominant FTD/TPI-related adverse events of grades 3 or 4 were neutropenia (13.0%), leukopenia (7.5%), and anemia (5.2%). Altogether, palliative FTD/TPI therapy in patients with pretreated mCRC was associated with prolonged survival, delayed progression, maintained health-related QoL, and manageable toxicity. Low metastatic burden and indolent disease were favorable prognostic factors for survival. TACTIC confirms the effectiveness and safety of FTD/TPI, highlighting its value in routine clinical practice.     

Safety and Preliminary Efficacy of Ramucirumab in Combination with FOLFOX4 in Patients with Advanced Hepatocellular Carcinoma: A Nonrandomized,Open‐Label,Phase Ib Study

Lessons Learned

• The combination of ramucirumab (8 mg/kg intravenous, day 1 every 2 weeks) and FOLFOX4 as first‐line treatment in patients with advanced hepatocellular carcinoma (HCC) was not sufficiently tolerated.
• Preliminary efficacy data suggest that the combination may provide clinical benefit to patients with HCC.
• Dose modification and patient selection should be considered for the future development of ramucirumab plus FOLFOX chemotherapy for advanced HCC.

BackgroundThe objective of this study was to investigate the safety, preliminary efficacy, pharmacokinetics, and immunogenicity of ramucirumab plus FOLFOX4 as first‐line treatment in patients with advanced hepatocellular carcinoma (HCC).MethodsPatients received ramucirumab (8 mg/kg) intravenously (IV) on day 1, followed by FOLFOX4 (oxaliplatin 85 mg/m² IV on day 1, folinic acid 200 mg/m² IV, bolus fluorouracil [5‐FU] 400 mg/m², and a continuous infusion of 5‐FU 600 mg/m² over 22 hours, on days 1 and 2) every 2 weeks. The primary endpoint was to assess the safety and tolerability of the combination therapy.ResultsEight patients (6 men, 2 women) were treated; all eight patients experienced at least one treatment‐emergent adverse event (TEAE) of grade ≥3. Dose‐limiting toxicities occurred in three patients (37.5%): hepatic hemorrhage (grade 4), blood bilirubin increased (grade 3), and febrile neutropenia (grade 3). Two patients discontinued study because of hepatic hemorrhage (grade 4) and blood bilirubin increase (grade 3). Six deaths occurred due to progressive disease, and no deaths due to TEAEs.ConclusionThere were no unexpected safety findings with ramucirumab plus FOLFOX4 based on the known safety and toxicity of this regimen. The combination was not sufficiently tolerated in patients with advanced HCC at the specified dose and schedule.     

Barriers to vaccination service delivery within general practice: opportunity to make a sustainable difference in Aboriginal child health?

Objective: To identify behavioural barriers of service provision within general practice that may be impacting the vaccination coverage rates of Aboriginal children in Perth, Western Australia (WA). Methods: A purposive developed survey was distributed to 316 general practices across Perth and three key informant interviews were conducted using a mixed‐methods approach. Results: Of the surveyed participants (n=101), 67.4% were unaware of the low vaccination coverage in Aboriginal children; 64.8% had not received cultural sensitivity training in their workplace and 46.8% reported having inadequate time to follow up overdue child vaccinations. Opportunistic vaccination was not routinely performed by 30.8% of participants. Key themes identified in the interviews were awareness, inclusion and cultural safety. Conclusion: Inadequate awareness of the current rates, in association with a lack of cultural safety training, follow‐up and opportunistic practice, may be preventing greater vaccination uptake in Aboriginal children in Perth. Cultural safety is a critical component of the acceptability and accessibility of services; lack of awareness may restrict the development of strategies designed to equitably address low coverage. Implications: The findings of this study provide an opportunity to raise awareness among clinicians in general practice and inform future strategies to equitably deliver targeted vaccination services to Aboriginal children.     

Gender equity: how do the forensic sciences fare?

ABSTRACT

Females are underrepresented in science, technology, engineering and mathematics (STEM) at all levels of society. Fewer females are completing STEM school subjects, graduating with STEM degrees, being employed as STEM professionals, and holding senior leadership and academic positions in STEM. However, unlike almost every other STEM discipline, the overall ratio of females is higher in many forensic science disciplines. For our sector, rather than having difficulty in attracting females, the bigger issue is how we retain and promote female talent. This complex issue is exacerbated by: gender pay gaps; family role expectations; lack of visible role models or mentors; discrimination and harassment; and bias during recruitment and promotion practices. We discuss barriers relevant for women in the forensic industry and offer potential solutions. These include flexible work arrangements, sponsorship programmes, and fostering and practising an inclusive workplace culture. Gender equity programmes and exemplar STEM organizations focused on a commitment to gender parity will be explored. Harnessing untapped female talent is as much a social justice issue as employing best practices for improving the quality, diversity and output of our forensic science workforce, and research and innovation strategies.