Comparison of three-weekly and six-weekly pembrolizumab United Kingdom prescribing practice for advanced and resected melanoma.

BACKGROUND: Pembrolizumab is approved for the treatment of advanced and resected melanoma and was originally licensed as a three-weekly infusion (Q3W). In April 2019, a six-weekly infusion schedule (Q6W) was also approved. We retrospectively reviewed pembrolizumab prescribing for patients with melanoma across multiple United Kingdom (UK) centres to compare the safety and efficacy of Q6W with Q3W in real-world clinical practice. METHODS: Case notes for melanoma patients treated with pembrolizumab between April 2019 and August 2020 at eight UK centres were reviewed. Prespecified baseline characteristics of the Q3W and Q6W cohorts were compared, as well as toxicity and efficacy outcomes. Prescribers were surveyed about their prescribing practice. RESULTS: Two hundred seventy-seven patients were included: 116 commenced Q3W and 161 commenced Q6W pembrolizumab. The proportion of Q6W prescriptions varied by the centre (range 32-88%). Patient factors associated with an increased likelihood of receiving Q3W over Q6W were preexisting autoimmune comorbidity (odds ratio [OR] 0.33; 95% confidence interval [CI] 0.12-0.82) and treatment for advanced (versus resected) disease (OR 0.54; 95%CI 0.33-0.90). Toxicity outcomes were broadly similar for Q6W and Q3W: 14.9% versus 15.5% ≥ grade 3 Common Terminology Criteria for Adverse Events. Estimated 12-month recurrence-free survival for adjuvantly treated patients was 78.9% for Q6W and 74.2% for Q3W (hazard ratio [HR] 0.93; 95%CI 0.50-1.73). Estimated 12-month progression-free survival for advanced patients was 41.8% for Q6W and 55.9% for Q3W (HR 1.21, 95%CI 0.67-2.18). CONCLUSIONS: Q6W is an appropriate option for administering pembrolizumab, given the opportunity to reduce the health service resource burden.

Improvements in the management of neutropenic sepsis: lessons learned from a district general hospital.

Neutropenic sepsis is a life-threatening condition with mortality rates reported to range between 2 and 21% in adults. It can occur following chemotherapy treatment, due to disease (such as haematological conditions affecting the bone marrow) and in patients on disease-modifying agents (such as patients receiving methotrexate for rheumatoid arthritis). Appropriate emergency treatment is essential and achieving intravenous antibiotic door-to-needle time of less than 1 hour is a key target. Shortfalls in the management of patients presenting to teams with limited expertise in this area were identified in the National Confidential Enquiry into Patient Outcome and Death report in 2008, leading to recommendations including the need for an acute oncology service (AOS) at all hospitals with either an emergency department or medical admissions unit. Practice at Weston General Hospital has been audited at three time points since 2008 (in 2008, 2011 and 2013-14) during which there have been several service developments relevant to the management of neutropenic sepsis, including the introduction of an AOS in June 2013. The percentage of patients in which intravenous antibiotic 1-hour door-to-needle time was achieved has improved from 14% (2008) to 31% (2011) to 79% (2013-14) and neutropenic sepsis mortality has decreased from 39% (2008) to 14% (2011) to 0% (2013-14).