Objective: Selpercatinib and pralsetinib are new targeted therapies used to treat patients with non-small cell lung cancer (NSCLC) due to RET gene rearrangements. The objective of this article is to review selpercatinib and pralsetinib in the context of RET-fusion-positive NSCLC. Data sources: The pivotal LIBRETTO-001 and ARROW trials were evaluated regarding the use of selpercatinib and pralsetinib as treatment for RET-fusion-positive NSCLC. Comparative studies, review articles and current studies on selpercatinib and pralsetinib in RET-fusion-positive NSCLC were searched on pubmed.org and scholar.google.com using “selpercatinib,” “pralsetinib,” and “NSCLC” as keywords. Product monographs were searched on google.ca and uptodate.com using the keywords “selpercatinib,” “pralsetinib,” and/or “monograph.” Data summary: Selpercatinib and pralsetinib are orally administered highly selective RET inhibitors approved by the FDA following the accelerated approvals granted due to the pivotal LIBRETTO-001 and ARROW trials which evaluated selpercatinib and pralsetinib, respectively. Both drugs have shown efficacy for brain metastases and are primarily metabolized by CYP3A4 through hepatic metabolism. The most common grade 3 or 4 adverse effects of selpercatinib were hypertension, increased ALT level, and increased AST level while for pralsetinib, it was neutropenia, hypertension, and anemia. The safety profile shows similarities in severity and tolerability but additional monitoring for QT prolongation in patients on selpercatinib is recommended, compared to the risks of interstitial lung disease or pneumonitis for patients on pralsetinib. Conclusions: Overall, the increased use of selpercatinib and pralsetinib has led to the implementation of these drugs in the clinical practice of healthcare professionals such as pharmacists.

Multi-criteria decision analysis (MCDA) is a value assessment tool designed to help support complex decision-making by incorporating multiple factors and perspectives in a transparent, structured approach. We developed an MCDA rating tool, consisting of seven criteria evaluating the importance and feasibility of conducting potential real-world evidence (RWE) studies aimed at addressing uncertainties stemming from initial cancer drug funding recommendations. In collaboration with the Canadian Agency for Drugs and Technologies in Health’s Provincial Advisory Group, a validation exercise was conducted to further evaluate the application of the rating tool using RWE proposals varying in complexity. Through this exercise, we aimed to gain insight into consensus building and deliberation processes and to identify efficiencies in the application of the rating tool. An experienced facilitator led a multidisciplinary committee, consisting of 11 Canadian experts, through consensus building, deliberation, and prioritization. A total of nine RWE proposals were evaluated and prioritized as low (n = 4), medium (n = 3), or high (n = 2) priority. Through an iterative process, efficiencies and recommendations to improve the rating tool and associated procedures were identified. The refined MCDA rating tool can help decision-makers prioritize important and feasible RWE studies for research and can enable the use of RWE for the life-cycle evaluation of cancer drugs.

The CanREValue Collaboration established the Reassessment & Uptake Working Group to develop a preliminary process to reassess funded cancer drugs in Canada. A simulated exercise was conducted to evaluate the proposed reassessment process using a real-world case. We invited 32 attendees including representatives from Health Canada and Health Technology Assessment (HTA) agencies, along with payers, clinicians, academics, and patient representatives. A case was developed using a real-world study on a publicly funded cancer drug. In facilitated group sessions, participants were asked to deliberate upon the evidence presented in the case to issue reassessment recommendations. Several themes were identified through the deliberation discussions. While the generalizability of real-world evidence (RWE) is perceived as a strength, trust in the RWE depends largely on the source of the real-world data. The attendees suggested several improvements to the proposed reassessment process including evidence requirement for reassessment, recommendation categories, and a priori study protocols. This exercise generated important insights on the evidence required for conducting reassessment and considerations for improvements of the proposed reassessment process. Building upon lessons from this exercise, future work would continue to refine the reassessment process as part of the overall CanREValue framework.

Background: Daratumumab is used in the treatment of relapsed multiple myeloma. Daratumumab infusion-related reactions can occur with the highest incidence on the first infusion. Methods: A retrospective review of all daratumumab infusions used as part of the DVd and DRd regimens for relapsed multiple myeloma was undertaken. The review of infusion-related reactions was conducted by reviewing the treatment room nursing note on the days that daratumumab was administered. If the patient experienced an infusion-related reaction, then the data captured included if the full dose was administered. Results: Daratumumab infusion-related reactions occurred most frequently on the first dose. The rates of infusion-related reactions using a split dose approach for daratumumab administration were lower than that reported in clinical trials. All of the infusion-related reactions were managed with appropriate interventions in the outpatient setting. The adoption of rapid infusion daratumumab beginning with cycle 2 of DVd and DRd was well tolerated. Conclusions: Our experience of daratumumab infusions using a split dose approach was associated with an infusion-related reaction rate in 28% of patients on cycle 1, day 1 of DVd and DRd regimens. All patients were able to complete full doses of daratumumab by utilizing split dose. The rates of daratumumab infusion-related reactions are highest on the first infusion. In addition, our adoption of rapid infusion daratumumab was safe.

Background: Recognition of anaphylaxis and differentiation from other infusion reactions in an oncology setting is imperative; epinephrine is the recommended treatment for anaphylaxis and should be administered immediately to patients in whom anaphylaxis is suspected. Trastuzumab has a potentially tremendous oncological benefit, and when hypersensitivity reactions occur, rechallenge with desensitization protocols has become more common. Oncology presents a unique situation in which repeat drug exposure after a serious adverse reaction is often warranted due to the mortality risk of untreated cancer—allergists can assist with both symptom assessment and risk mitigation. Case presentation: This case showcases successful desensitization in a 43-year-old female with locally advanced HER2-positive breast cancer following a severe anaphylactic reaction to trastuzumab, in which epinephrine was not administered. We report the establishment of the Medical Oncology and Allergy Clinic: Canada’s first multidisciplinary clinic aimed at expediting the assessment and management of oncology patients with adverse drug reactions (including chemotherapy, contrast media, antimicrobials) and those with primary and acquired immunodeficiency. Conclusions: We propose this multidisciplinary clinic model as a treatment framework moving forward, with the goal of continuing first-line therapies in cancer patients who develop drug-hypersensitivity (i.e., through desensitization). This case highlights the unmet need for a multidisciplinary approach to the management of oncology patients who experience hypersensitivity reactions.

The Canadian Real-world Evidence for Value of Cancer Drugs (CanREValue) collaboration developed an MCDA rating tool to assess and prioritize potential post-market real-world evidence (RWE) questions/uncertainties emerging from public drug funding decisions in Canada. In collaboration with a group of multidisciplinary stakeholders from across Canada, the rating tool was developed following a three-step process: (1) selection of criteria to assess the importance and feasibility of an RWE question; (2) development of rating scales, application of weights and calculating aggregate scores; and (3) validation testing. An initial MCDA rating tool was developed, composed of seven criteria, divided into two groups. Group A criteria assess the importance of an RWE question by examining the (1) drug’s perceived clinical benefit, (2) magnitude of uncertainty identified, and (3) relevance of the uncertainty to decision-makers. Group B criteria assess the feasibility of conducting an RWE analysis including the (1) feasibility of identifying a comparator, (2) ability to identify cases, (3) availability of comprehensive data, and (4) availability of necessary expertise and methodology. Future directions include partnering with the Canadian Agency for Drugs and Technology in Health’s Provincial Advisory Group for further tool refinement and to gain insight into incorporating the tool into drug funding deliberations.