Explore the vast range of titles available.

Immune checkpoint inhibitors have revolutionised cancer treatment by offering durable responses to many patients with solid and haematological cancers. The high prices and increasing use of immune checkpoint inhibitors put considerable strain on health-care budgets globally. This financial strain could jeopardise patients’ access to these anti-cancer therapies. However, substantial evidence suggests that immune checkpoint inhibitors are being administered at doses that exceed the minimum dose required for maximum anti-tumour efficacy. Therefore, investigating and implementing the most cost-effective dosing strategies for immune checkpoint inhibitors are urgently necessary. This Personal View provides an overview of existing data on immune checkpoint inhibitor pharmacology and (novel) dosing strategies for anti-PD-1 therapy with nivolumab and pembrolizumab, with a special focus on cost-effectiveness and saving potential. Furthermore, specific recommendations to guide health-care professionals are provided, through the process of prescribing, rounding, preparing, and administering nivolumab and pembrolizumab in the most practical and cost-effective way possible.

Background Recent studies have underscored the potential of innovative administration methods to mitigate the capacity burden on healthcare systems, without compromising the quality of care. This study assessed and compared the resource utilization and associated costs of two distinct administration modes of immune checkpoint inhibitors: the innovative elastomeric pump and conventional intravenous infusion. This comparison can inform sustainable healthcare practices and healthcare decision-making to optimize treatment efficiency in an era of escalating healthcare demands. Methods In this micro-costing study, data on resource use and time allocation for drug preparation and administration were collected using an observational, non-interventional study design. Data were registered at the oncology daycare unit and hospital pharmacy. Cost categories included drug acquisition, disposable materials, healthcare professional time for drug administration, drug preparation, and patient time spent at the oncology day care unit. Results Drug administration through the elastomeric pump resulted in substantially lower healthcare costs when compared to conventional infusion, particularly due to reduced labor and chair time. The elastomeric pump reduced the total chair time by 78% and nurse time by 55%. Total average costs (excluding drug costs) were €103,47 and €77.99 for conventional infusion and the elastomeric pump, respectively, showcasing potential savings of €25.48 ( P  < 0.001) per administration. Conclusions This study demonstrated that the elastomeric pump not only offers substantial cost savings but also enhances the treatment capacity of the oncology day care unit. These findings support the adoption of the elastomeric pump in clinical settings as a cost-saving and efficient alternative to conventional infusion. Trial registration This study has been registered in the National Trial Register (NTR), with the reference number NTR NL9473. Registration date: 05-05-2021.

Background Ranitidine, a histamine 2 blocker, is the standard of care to prevent hypersensitivity reactions (HSRs) caused by paclitaxel infusion. However, the added value of ranitidine in this premedication regimen is controversial. Therefore, we compared the incidence of HSRs during paclitaxel treatment between a standard regimen including ranitidine and a regimen without ranitidine. Methods This prospective, pre–post interventional, non-inferiority study compared the standard premedication regimen ( N  = 183) with dexamethasone, clemastine and ranitidine with a premedication regimen without ranitidine ( N  = 183). The primary outcome was the incidence of HSR grade ≥3. Non-inferiority was determined by checking whether the upper bound of the two-sided 90% confidence interval (CI) for the difference in HSR rates excluded the +6% non-inferiority margin. Results In both the pre-intervention (with ranitidine) and post-intervention (without ranitidine) group 183 patients were included. The incidence of HSR grade ≥3 was 4.4% ( N  = 8) in the pre-intervention group and 1.6% ( N  = 3) in the post-intervention group: difference −2.7% (90% CI: −6.2 to 0.1). Conclusions As the upper boundary of the 90% CI does not exceed the predefined non-inferiority margin of +6%, it can be concluded that a premedication regimen without ranitidine is non-inferior to a premedication regimen with ranitidine. Clinical Trial Registration www.trialregister.nl ; NL8173.

Ranitidine, a histamine 2 blocker, is the standard of care to prevent hypersensitivity reactions (HSRs) caused by paclitaxel infusion. However, the added value of ranitidine in this premedication regimen is controversial. Therefore, we compared the incidence of HSRs during paclitaxel treatment between a standard regimen including ranitidine and a regimen without ranitidine. This prospective, pre-post interventional, non-inferiority study compared the standard premedication regimen (N = 183) with dexamethasone, clemastine and ranitidine with a premedication regimen without ranitidine (N = 183). The primary outcome was the incidence of HSR grade ≥3. Non-inferiority was determined by checking whether the upper bound of the two-sided 90% confidence interval (CI) for the difference in HSR rates excluded the +6% non-inferiority margin. In both the pre-intervention (with ranitidine) and post-intervention (without ranitidine) group 183 patients were included. The incidence of HSR grade ≥3 was 4.4% (N = 8) in the pre-intervention group and 1.6% (N = 3) in the post-intervention group: difference -2.7% (90% CI: -6.2 to 0.1). As the upper boundary of the 90% CI does not exceed the predefined non-inferiority margin of +6%, it can be concluded that a premedication regimen without ranitidine is non-inferior to a premedication regimen with ranitidine. www.trialregister.nl ; NL8173.

PD-1/PD-L1-blockade immunotherapies have limited efficacy in the treatment of muscle-invasive bladder cancer (MIBC) and metastatic urothelial carcinoma. Here, we show that KLRC1 (NKG2A) expression associates with improved survival and responsiveness to PD-L1 blockade immunotherapy in CD8Ahigh bladder tumors. The loss of antigen presentation is a common mechanism for tumor escape in bladder cancer. NKG2A+ CD8 T cells are able to circumvent HLA-ABC loss through TCR-independent cytotoxicity, which is partly mediated by DNAM-1. In bladder tumors, NKG2A is acquired on a subset of PD-1+ CD8 T cells, alongside stronger tissue-residency memory features, TCR-independent cytotoxicity and evidence of recent proliferation. HLA-E is low but variably expressed on bladder tumors. When expressed, NKG2A+ CD8 T cell anti-tumor responses to HLA-ABC-deficient tumors are inhibited and partly restored upon NKG2A blockade. Overall, our study identifies an alternative path for CD8 T cell exhaustion, that is mediated by NKG2A upregulation and TCR-independent cytotoxicity. Competing Interest Statement L.W., R.P.S., and J.Z. are employees of Sema4. A.H. receives research funds from Zumutor Biologics; and is on the advisory boards of HTG Molecular Diagnostics, Immunorizon, and Takeda. N.B. is an extramural member of the Parker Institute for Cancer Immunotherapy; receives research funds from Regeneron, Harbor Biomedical, DC Prime, and Dragonfly Therapeutics; and is on the advisory boards of Neon Therapeutics, Novartis, Avidea, Boehringer Ingelheim, Rome Therapeutics, Rubius Therapeutics, Roswell Park Comprehensive Cancer Center, BreakBio, Carisma Therapeutics, CureVac, Genotwin, BioNTech, Gilead Therapeutics, Tempest Therapeutics, and the Cancer Research Institute.