BackgroundExpensive novel anticancer drugs put a serious strain on healthcare budgets, and the associated drug expenses limit access to life-saving treatments worldwide.ObjectiveWe aimed to develop... Show moreBackgroundExpensive novel anticancer drugs put a serious strain on healthcare budgets, and the associated drug expenses limit access to life-saving treatments worldwide.ObjectiveWe aimed to develop alternative dosing regimens to reduce drug expenses.MethodsWe developed alternative dosing regimens for the following monoclonal antibodies used for the treatment of lung cancer: amivantamab, atezolizumab, bevacizumab, durvalumab, ipilimumab, nivolumab, pembrolizumab, and ramucirumab; and for the antibody-drug conjugate trastuzumab deruxtecan. The alternative dosing regimens were developed by means of modeling and simulation based on the population pharmacokinetic models developed by the license holders. They were based on weight bands and the administration of complete vials to limit drug wastage. The resulting dosing regimens were developed to comply with criteria used by regulatory authorities for in silico dose development.ResultsWe found that alternative dosing regimens could result in cost savings that range from 11 to 28%, and lead to equivalent pharmacokinetic exposure with no relevant increases in variability in exposure.ConclusionsDosing regimens based on weight bands and the use of complete vials to reduce drug wastage result in less expenses while maintaining equivalent exposure. The level of evidence of our proposal is the same as accepted by regulatory authorities for the approval of alternative dosing regimens of other monoclonal antibodies in oncology. The proposed alternative dosing regimens can, therefore, be directly implemented in clinical practice. Show less
Background: It has been proven that intraoperative prostate-specific membrane antigen (PSMA)-targeted radioguidance is valuable for the detection of prostate cancer (PCa) lesions during open... Show moreBackground: It has been proven that intraoperative prostate-specific membrane antigen (PSMA)-targeted radioguidance is valuable for the detection of prostate cancer (PCa) lesions during open surgery. Rapid extension of robot-assisted, minimally invasive surgery has increased the need to make PSMA-radioguided surgery (RGS) robot-compliant.Objective: To evaluate whether the miniaturized DROP-IN gamma probe facilitates translation of PSMA-RGS to robotic surgery in men with recurrent PCa.Design, setting, and participants: This prospective feasibility study included 20 patients with up to three pelvic PCa recurrences (nodal or local) on staging PSMA positron emission tomography (PET) after previous curative-intent therapy.Surgical procedure: Robot-assisted PSMA-RGS using the DROP-IN gamma probe was carried out 19-23 h after intravenous injection of (99m)technetium PSMA-Investigation & Surgery (Tc-99m-PSMA-I&S).Measurements: The primary endpoint was the feasibility of robot-assisted PSMA-RGS. Secondary endpoints were a comparison of the radioactive status (positive or negative) of resected specimens and final histopathology results, prostate-specific antigen (PSA) response following PSMA-RGS, and complications according to the Clavien-Dindo classification.Results and limitations: Using the DROP-IN probe, 19/21 (90%) PSMA-avid lesions could be resected robotically. On a per-lesion basis, the sensitivity and specificity of robot-assisted PSMA-RGS was 86% and 100%, respectively. A prostate-specific antigen (PSA) reduction of >50% and a complete biochemical response (PSA <0.2 ng/ml) were seen in 12/18 (67%) and 4/18 (22%) patients, respectively. During follow-up of up to 15 mo,* Corresponding author. Department of Urology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands. Tel. +31 205126988. E-mail address: h.d.barros@nki.nl (H.A. de Barros) Show less
Monoclonal antibodies (Mabs) have become key drugs in cancer treatment, either as targeted therapies or more recently as immune checkpoint inhibitors (ICIs). The fact that only some patients... Show moreMonoclonal antibodies (Mabs) have become key drugs in cancer treatment, either as targeted therapies or more recently as immune checkpoint inhibitors (ICIs). The fact that only some patients benefit from these drugs poses the usual question in the field of onco-hematology: that of the benefit of individual dosing and the potential of therapeutic drug monitoring (TDM) to carry out this individualization. However, Mabs present unique pharmacological characteristics for TDM, and the pharmacokinetic-pharmacodynamic relationship observed should be interpreted differently than that observed for conventional drugs and small molecules. This pharmacology practice review has been summarized from a public debate between the authors at the International TDM and Clinical Toxicology meeting in Banff, 2020, regarding the potential roles of TDM in the Mab/ICI setting. Show less
