Oncology Drug Research Articles

Cumulative Dosage of Intrathecal Chemotherapy Agents Predicts White Matter Integrity in Long-Term Survivors of Acute Lymphoblastic Leukemia: A PETALE Study.

Acute lymphoblastic leukemia (ALL) stands as the most prevalent form of pediatric cancer in North America, with a current five-year survival rate of 85%. While more children achieved ALL remission and transition into adulthood, the prevalence of long-term treatment-related effects, especially neurocognitive sequelae, remains significant. This study pursues two objectives. Firstly, it investigates if Magnetization Transfer Ratio (MTR), a method assessing myelin integrity, is sensitive to white matter (WM) microstructural changes in long-term ALL survivors and whether these relate to cognitive impairments. Secondly, it examines the dose-related effects of chemotherapy agents on the MTR and its relationship to other risk factors such as female sex, early age diagnosis, and cranial radiotherapy. Magnetization transfer imaging was utilized to assess WM integrity in 35 survivors at a mean of 18.9 years after the onset of ALL (range since diagnosis: 6.9-26.8). Additionally, 21 controls matched for age, sex, and education level, with no history of cancer, were included. MTR was extracted from both the entire brain's WM and the corpus callosum through semi-automated procedures. The results indicated lower MTR means in survivors, which is linked to cognitive function. Negative associations between MTR means and intrathecal agents' (MTX, cytarabine, and hydrocortisone) cumulative doses received were highlighted. This study offers valuable insights into the connections between myelin deterioration, cognitive impairment, and the implications of IT chemotherapy, enhancing our understanding of ALL survivorship dynamics. It underscores MTR's relevance in monitoring neurotoxicity during oncological drug follow-up examinations.

Oral docetaxel plus encequidar – A pharmacokinetic model and evaluation against IV docetaxel

The development of optimized dosing regimens plays a crucial role in oncology drug development. This study focused on the population pharmacokinetic modelling and simulation of docetaxel, comparing the pharmacokinetic exposure of oral docetaxel plus encequidar (oDox + E) with the standard of care intravenous (IV) docetaxel regimen. The aim was to evaluate the feasibility of oDox + E as a potential alternative to IV docetaxel. The article demonstrates an approach which aligns with the FDA’s Project Optimus which aims to improve oncology drug development through model informed drug development (MIDD). The key question answered by this study was whether a feasible regimen of oDox + E existed. The purpose of this question was to provide an early GO / NO-GO decision point to guide drug development and improve development efficiency. Methods: A stepwise approach was employed to develop a population pharmacokinetic model for total and unbound docetaxel plasma concentrations after IV docetaxel and oDox + E administration. Simulations were performed from the final model to assess the probability of target attainment (PTA) for different oDox + E dose regimens (including multiple dose regimens) in relation to IV docetaxel using AUC over effective concentration (AUCOEC) metric across a range of effective concentrations (EC). A Go / No-Go framework was defined—the first part of the framework assessed whether a feasible oDox + E regimen existed (i.e., a PTA ≥ 80%), and the second part defined the conditions to proceed with a Go decision. Results: The overall population pharmacokinetic model consisted of a 3-compartment model with linear elimination, constant bioavailability, constant binding mechanics, and a combined error model. Simulations revealed that single dose oDox + E regimens did not achieve a PTA greater than 80%. However, two- and three-dose regimens at 600 mg achieved PTAs exceeding 80% for certain EC levels. Conclusion: The study demonstrates the benefits of MIDD using oDox + E as a motivating example. A population pharmacokinetic model was developed for the total and unbound concentration in plasma of docetaxel after administration of IV docetaxel and oDox + E. The model was used to simulate oDox + E dose regimens which were compared to the current standard of care IV docetaxel regimen. A GO / NO-GO framework was applied to determine whether oDox + E should progress to the next phase of drug development and whether any conditions should apply. A two or three-dose regimen of oDox + E at 600 mg was able to achieve non-inferior pharmacokinetic exposure to current standard of care IV docetaxel in simulations. A Conditional GO decision was made based on this result and further quantification of the “effective concentration” would improve the ability to optimise the dose regimen.

On the use of RWD in support of regulatory submission in drug development

ABSTRACT For the approval of a drug product, the United States Food and Drug Administration requires substantial evidence (SE) regarding effectiveness and safety of the test drug to be provided. In recent years, the use of real-world data in support of regulatory submission of pharmaceutical development has received much attention, and real-world evidence (RWE) is treated as complementary to SE by evaluating the real-world performance of the test treatment. In this article, we start by summarizing current regulatory perspectives on drug evaluation and some potential challenges in using RWE. To test for superiority in co-primary endpoints, a two-stage hybrid RCT/RWS adaptive design that combines randomized control trial for providing SE and real-world study for generating RWE is proposed. We use superiority in effectiveness and non-inferiority in safety as an example to illustrate how to implement this design. Numerical studies have shown that the proposed design has merits in reducing the required sample size compared with traditional co-primary endpoint tests while maintaining statistical power and controlling type I error inflation. The proposed design can be implemented in drug development considering co-primary endpoints, especially for oncology and rare disease drug development.

PDE5 inhibitors against cancer via mediating immune cells in tumor microenvironment: AI‐based approach for future drug repurposing exploration

AbstractPhosphodiesterase‐5 (PDE5) inhibitors are used clinically for the treatment of erectile dysfunction, pulmonary arterial hypertension, and other urological diseases. Emerging evidences have suggested the therapeutic capacity of PDE5 inhibitors as the repurposed drugs in oncology. However, the essential immune function of PDE5 inhibitors against cancer in tumor microenvironment (TME) remains unclear. This review aimed to summarize the recent advances regarding the repurposing of PDE5 inhibitors as anti‐cancer agents for cancer management to enhance the anti‐tumor immune response by mediating various immune cells, which included the myeloid‐derived suppressor cells, macrophages, T cells, fibroblasts, and natural killer cells in TME. Moreover, artificial intelligence (AI), as a new approach, is composed of traditional machine learning and deep learning methods and could be potentially used to identify the targets of immune cells in TME and predict the efficacy for repurposed drug toward malignancies. In summary, these endeavors provide novel insights into the comprehensive strategies for PDE5 inhibitors mediating immune cells against cancer and AI‐based approach for future drug repurposing exploration.

Japan’s contribution to an ongoing global pediatric cancer clinical trial: The experience of the National Cancer Center Hospital (NCCH) in Tokyo

Compared to Europe and the United States, where the development of pediatric oncology drugs is mandated by law, Japan hosts fewer clinical trials. This can lead to a significant drug lag, especially in the case of treatments for pediatric solid tumors. Notably, regulatory authorities and the government have initiated discussions on strategies to mitigate Japan’s drug lag problem in pediatric oncology. Over the past decade, we have actively sought opportunities to participate in international collaborative clinical trials through Japan’s involvement in ACCELERATE and its predecessor organizations. This approach has aimed to address the issue above, coinciding with the ongoing centralization of medical care and advancements in genomic medicine, among other systems that support pediatric cancer care in Japan. Inspired by the ACCELERATE initiatives and in response to patient advocacy groups’ requests for new pediatric oncology drugs, Japan established its inaugural pediatric oncology support platform in 2021, the National Childhood Cancer Consortium (N3C). N3C comprises patient advocacy groups, industries, and academia. This work outlines the current status of pediatric drug development in Japan and highlights the initial successful experience of NCCH’s participation in a global clinical trial through ACCELERATE resulting in rapid preparation and patient recruitment. Participation of Asian countries including Japan in global collaborative clinical trials may benefit both pharmaceutical companies and the participating countries partnering to advance the development of pediatric oncology drugs.

Güncel Kılavuzlara Göre Aspirinin Birincil Korunmadaki Rolü: Aile Hekimleri için Öneriler

Family physicians, who are the leaders of primary health care institutions that patients can access easily, should recommend aspirin to patients with suitable indications for primary or secondary protection by evaluating the benefit-harm relationship via the principle of "Primum non nocere". Studies which were conducted in Turkish primary care settings mentioned that there is an irrational and inappropriate use of aspirin in the primary prevention of atherosclerotic cardiovascular diseases. Aspirin has a role in the primary prevention of cardiovascular diseases, in reducing the incidence of colorectal cancer, in protection related to increased thrombosis risk by some oncology drugs, and in protection from pregnancy complications. Recommendations from current guidelines will lead the way to family physicians regarding the use of aspirin.

Impact of Systemic Delays for Patient Access to Oncology Drugs on Clinical, Economic, and Quality of Life Outcomes in Canada: A Call to Action.

Canada has one of the most complex and rigorous drug approval and public reimbursement processes and is, unfortunately, one of the countries with the longest delays in drug access. To assess the overall impact of systemic delays in access to cancer therapy, a targeted literature review (TLR) was performed to identify studies associated with the clinical, economic, and quality of life impacts of delayed access to oncology drugs. Using MEDLINE/PubMed databases and snowballing, four unique records met the eligibility criteria. Results revealed that clinical outcomes were the most impacted by systemic delays in access to oncology drugs (e.g., life years lost, overall survival, and progression-free survival). The four articles retrieved by the TLR specifically illustrated that a substantial number of life years could potentially be saved by increasing systemic efficiency regarding the development, approval, and reimbursement processes of new drugs for advanced malignancies. It is imperative that initiatives are put in place to improve the performance and speed of Canadian drug regulatory and health technology assessment (HTA) processes, especially for new cancer therapeutics. The proposed solutions in this paper include better coordination between HTA and Canadian payers to harmonize coverage decisions, international collaborations, information sharing, and national standards for timeliness in oncology drug access.

Comparison of prior authorization across insurers: cross sectional evidence from Medicare Advantage

ObjectiveTo measure and compare the scope of US insurers’ policies for prior authorization (PA), a process by which insurers assess the necessity of planned medical care, and to quantify differences...

HTA regulation: how is Italy moving?

Within the European evolutionary framework concerning citizens’ health, the focus shifts to the new HTA regulation, set to alter processes and influence decision-making at the individual country level regarding reimbursement and pricing. The ambitious goal of achieving faster and more uniform access will significantly reshape the evaluative model stabilized over the years, characterized by the creation of different rules and processes among member states and diverse output timelines across the countries. The imminent adoption of a more collaborative process necessitates member countries and companies to address several steps to ensure a smooth transition without penalizing the unique aspects of individual countries or impeding real access. Italy, actively participating in European preparatory activities with AIFA, faces challenges in adapting its formal process due to AIFA’s ongoing reform since November 2022, which is not yet materialized. National-level companies heavily depend on leadership and involvement rules from their HTA agencies, with the risk that agencies with more established engagement models with external stakeholders may present themselves on January 12, 2025, the start date of the new process for oncological and ATMP drugs, better prepared and may excel in designing scoping meetings and in formulating PICO. Therefore, the activation of a country culture of HTA and a robust and extended “readiness” phase involving all stakeholders are desirable, along with the establishment of collaboration networks with universities and scientific societies to make valuable knowledge and qualified resources more readily available, crucial element for the delicate transition from the old to the new evaluative system.

Evaluation of changes in the clinical benefits of oncology drugs over time following reimbursement using the ASCO-VF and the ESMO-MCBS

PurposeThis study aims to estimate changes in the value of oncology drugs over time from initial data of the reimbursement decisions to subsequent publications in Korea, using two value frameworks.MethodsWe retrieved primary publications assessed for reimbursement between 2007 and July 2021 from the decision documents of Health Insurance Review and Assessment and subsequent publications made available following reimbursement decision from ClinicalTrials.Gov and PubMed databases. Changes in the clinical benefit scores were assessed using the American Society of Clinical Oncology Value Framework (ASCO-VF) and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). A paired t test was performed to test whether there was a difference in the scores between primary and subsequent publications.ResultsOf 73 anticancer product/indication pairs, 45 (61.6%) had subsequent publications, of which 62.5% were released within 1 year of reimbursement decision. The mean ESMO-MCBS and ASCO-VF Net Health Benefit scores increased from primary to subsequent publications, although the differences were not significant. The mean ASCO-VF bonus score significantly increased from 15.91 to 19.09 (p = 0.05). The ESMO-MCBS and bonus scores increased by 0.25 and 0.21, respectively, and the bonus score had a greater impact on the ESMO-MCBS score than the preliminary score did.ConclusionThe value of drugs demonstrated in subsequent publications varies considerably among oncology drugs, depending on uncertainty associated with the initial evidence and the availability of updated evidence. As decision-making in the face of uncertainty becomes more prevalent, the value frameworks can serve as simple screening tools for re-evaluation in these cases.

Using imaging modalities to predict nanoparticle distribution and treatment efficacy in solid tumors: The growing role of ultrasound.

Nanomedicine in oncology has not had the success in clinical impact that was anticipated in the early stages of the field's development. Ideally, nanomedicines selectively accumulate in tumor tissue and reduce systemic side effects compared to traditional chemotherapeutics. However, this has been more successful in preclinical animal models than in humans. The causes of this failure to translate may be related to the intra- and inter-patient heterogeneity of the tumor microenvironment. Predicting whether a patient will respond positively to treatment prior to its initiation, through evaluation of characteristics like nanoparticle extravasation and retention potential in the tumor, may be a way to improve nanomedicine success rate. While there are many potential strategies to accomplish this, prediction and patient stratification via noninvasive medical imaging may be the most efficient and specific strategy. There have been some preclinical and clinical advances in this area using MRI, CT, PET, and other modalities. An alternative approach that has not been studied as extensively is biomedical ultrasound, including techniques such as multiparametric contrast-enhanced ultrasound (mpCEUS), doppler, elastography, and super-resolution processing. Ultrasound is safe, inexpensive, noninvasive, and capable of imaging the entire tumor with high temporal and spatial resolution. In this work, we summarize the in vivo imaging tools that have been used to predict nanoparticle distribution and treatment efficacy in oncology. We emphasize ultrasound imaging and the recent developments in the field concerning CEUS. The successful implementation of an imaging strategy for prediction of nanoparticle accumulation in tumors could lead to increased clinical translation of nanomedicines, and subsequently, improved patient outcomes. This article is categorized under: Diagnostic Tools In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery Emerging Technologies.

Challenges and opportunities in oncology drug development and clinical research in China

As one of the world's most populous countries, China bears a heavy burden and a broad spectrum of cancers, including unique types, providing a unique environment for drug research and development. In recent years, China has leapt forward in oncology drug development and clinical trials, presenting new opportunities and challenges.

Oncologic drug repository programs in the United States: a review and comparison.

As cancer affects 40% of all Americans during their lifetime, the financial burden of cancer care represents a significant contribution towards the overall cost of health care in the United States. Cancer drug repository programs offer a unique solution for patients who have limited financial ability to access medications while reducing medical waste. We reviewed all state legislation in the United States regarding cancer drug repository programs. Five states have oral anticancer drug (OACD)-specific drug repository programs, while 28 states have generalized drug repository programs. Iowa's statewide, mail-order OACD repository program is the preeminent example of an effective and efficient program, which should be replicated across the country. Many states have passed legislation allowing for drug repository programs but have struggled to translate such legislation into active programs due to lack of funding and management. We offer recommendations across policy, manufacturing, institutional, health care professional, and patient domains in order provide optimal patient care.

Added benefit and revenues of oncology drugs approved by the European Medicines Agency between 1995 and 2020: retrospective cohort study

ObjectivesTo evaluate the added benefit and revenues of oncology drugs, explore their association, and investigate potential discrepancies between added benefit and revenues across different approval pathways of the European Medicines...

Concurrent inhibition of pBADS99 synergistically improves MEK inhibitor efficacy in KRASG12D-mutant pancreatic ductal adenocarcinoma

Therapeutic targeting of KRAS-mutant pancreatic ductal adenocarcinoma (PDAC) has remained a significant challenge in clinical oncology. Direct targeting of KRAS has proven difficult, and inhibition of the KRAS effectors have shown limited success due to compensatory activation of survival pathways. Being a core downstream effector of the KRAS-driven p44/42 MAPK and PI3K/AKT pathways governing intrinsic apoptosis, BAD phosphorylation emerges as a promising therapeutic target. Herein, a positive association of the pBADS99/BAD ratio with higher disease stage and worse overall survival of PDAC was observed. Homology-directed repair of BAD to BADS99A or small molecule inhibition of BADS99 phosphorylation by NCK significantly reduced PDAC cell viability by promoting cell cycle arrest and apoptosis. NCK also abrogated the growth of preformed colonies of PDAC cells in 3D culture. Furthermore, high-throughput screening with an oncology drug library to identify potential combinations revealed a strong synergistic effect between NCK and MEK inhibitors in PDAC cells harboring either wild-type or mutant-KRAS. Mechanistically, both mutant-KRAS and MEK inhibition increased the phosphorylation of BADS99 in PDAC cells, an effect abrogated by NCK. Combined pBADS99-MEK inhibition demonstrated strong synergy in reducing cell viability, enhancing apoptosis, and achieving xenograft stasis in KRAS-mutant PDAC. In conclusion, the inhibition of BADS99 phosphorylation enhances the efficacy of MEK inhibition, and their combined inhibition represents a mechanistically based and potentially effective therapeutic strategy for the treatment of KRAS-mutant PDAC.

Assessment of potential drug-drug interactions in hospitalized cancer patients.

Drug-drug interactions (DDIs) pose a significant threat to patients with cancer, resulting in several adverse events in an oncology setting. Our study aims to identify potential DDIs in inpatient oncology wards, assess their severity, and provide recommendations to avoid these interactions. This prospective study was conducted in 79 hospitalized cancer patients over a period of 9 months (from August 2021 to May 2022) at the Amrita Institute of Medical Sciences, Kochi receiving at least two oncological or non-oncological drugs for 5 days. Significant differences were found in drug count (61.6% vs. 38.4%), hospitalization duration (63.1% vs. 36.9%), and medications for comorbidities (63% vs. 37%) between patients with and without DDIs (p < 0.001, <0.001, and 0.01, respectively). The study identified 321 DDIs, with 14 (4.4%) X interactions, 93 (30%) D interactions, 161 (50%) C interactions, and 53 (15.6%) B interactions. Severity-wise, 76 (23.7%) were major, 190 (59.1%) were moderate, and 55 (17.2%) were minor. Our study showed that drug count, medications for comorbidities, and hospitalization duration significantly increase the risk of DDIs in hospitalized oncology patients. Around 96.4% of recommendations for potential interactions were accepted and implemented, highlighting the huge opportunities and requirements for improvement, implementation, and management of drug interactions in oncology settings.

Engineering Biomaterials to Model Immune-Tumor Interactions In Vitro.

Engineered biomaterial scaffolds are becoming more prominent in research laboratories to study drug efficacy for oncological applications in vitro, but do they have a place in pharmaceutical drug screening pipelines? The low efficacy of cancer drugs in phase II/III clinical trials suggests that there are critical mechanisms not properly accounted for in the pre-clinical evaluation of drug candidates. Immune cells associated with the tumor may account for some of these failures given recent successes with cancer immunotherapies; however, there are few representative platforms to study immune cells in the context of cancer as traditional 2D culture is typically monocultures and humanized animal models have a weakened immune composition. Biomaterials that replicate tumor microenvironmental cues may provide a more relevant model with greater in vitro complexity. In this review, the authors explore the pertinent microenvironmental cues that drive tumor progression in the context of the immune system, discuss how these cues can be incorporated into hydrogel design to culture immune cells, and describe progress toward precision oncological drug screening with engineered tissues.

The patient perspective on dose optimization for anticancer treatments: A new era of cancer drug dosing-Challenging the "more is better" dogma.

The Patient-Centered Dosing Initiative, a patient-led effort advocating for a paradigm shift in determining cancer drug dosing strategies, pioneers a departure from traditional oncology drug dosing practices. Historically, oncology drug dosing relies on identifying the maximum tolerated dose through phase 1 dose escalation methodology, favoring higher dosing for greater efficacy, often leading to higher toxicity. However, this approach is not universally applicable, especially for newer treatments like targeted therapies and immunotherapies. Patient-Centered Dosing Initiative challenges this "more is better" ethos, particularly as metastatic breast cancer patients themselves, as they not only seek longevity but also a high quality of life since most metastatic breast cancer patients stay on treatment for the rest of their lives. Surveying 1221 metastatic breast cancer patients and 119 oncologists revealed an evident need for flexible dosing strategies, advocating personalized care discussions based on patient attributes. The survey results also demonstrated an openness toward flexible dosing and a willingness from both patients and clinicians to discuss dosing as part of their care. Patient-centered dosing emphasizes dialogue between clinicians and patients, delving into treatment efficacy-toxicity trade-offs. Similarly, clinical trial advocacy for multiple dosing regimens encourages adaptive strategies, moving away from strict adherence to maximum tolerated dose, supported by recent research in optimizing drug dosages. Recognizing the efficacy-effectiveness gap between clinical trials and real-world practice, Patient-Centered Dosing Initiative underscores the necessity for patient-centered dosing strategies. A focus on individual patient attributes aligns with initiatives like Project Optimus and Project Renewal, aiming to optimize drug dosages for improved treatment outcomes at both the pre- and post-approval phases. Patient-Centered Dosing Initiative's efforts extend to patient education, providing tools to initiate dosage-related conversations with physicians. In addition, it emphasizes physician-patient dialogues and post-marketing studies as essential in determining optimal dosing and refining drug regimens. A dose-finding paradigm prioritizing drug safety, tolerability, and efficacy benefits all stakeholders, reducing emergency care needs and missed treatments for patients, aligning with oncologists' and patients' shared goals. Importantly, it represents a win-win scenario across healthcare sectors. In summary, the Patient-Centered Dosing Initiative drives transformative changes in cancer drug dosing, emphasizing patient well-being and personalized care, aiming to enhance treatment outcomes and optimize oncology drug delivery.

Evaluation of technologies for oncology medicines: how value is assessed

Pricing or understanding the value of a technology is a very complex activity, after all, valuation is a multidisciplinary activity. This activity is inserted in the broad context of science, technology and innovation, which requires knowledge of several tools. Therefore, this manuscript aims to answer which technology valuation models are applicable, in technology transfer, in the oncology drugs sector. To achieve success, a documentary study was carried out, mapping the main manuscripts focused on this topic. The research was carried out through surveys in the Scopus database and VOSviewer was used to formulate the citation network. It was concluded, in terms of results, that analytical methods are best applied to the proposed objective, it was also possible to understand that valuation is not a single process, but a set of criteria that allows the analyst to know the various methods and various possibilities application of methodologies in the context of technology transfer.

(380) The Effect of Contemporary Oncologic Agents on Fertility Outcomes: A Review of the Literature

Abstract Introduction There is a growing number of referrals to urologists for oncofertility inquiries and concerns. Contemporary oncologic agents and their effect on fertility outcomes remain poorly understood. No study to date has evaluated the most common chemotherapeutic, immunologic, and targeted therapies seen by urologists and assessed their respective impacts on fertility. Objective We evaluated the effect of common contemporary chemotherapy, immunotherapy, and targeted therapy regimens on fertility outcomes. Methods We performed a single institutional review of all oncologic drugs taken by patients in the hematology/oncology clinic over the past five years (April, 2018- April, 2023). Agents were defined as contemporary if approval was received by the Food and Drug Administration 2006 or later. A review of the literature was conducted using PubMed to evaluate the effects on fertility for each drug. The MESH terms included agents [common name] OR [brand name] AND [sperm] OR [fertility] OR [infertility] OR [pregnancy] OR [birth] OR [reproductive] OR [reproduction] OR [ovarian] OR [testicular]. Search results for each agent were classified as “fertility impacted” or “fertility not impacted”. Studies were excluded if the primary aim or. secondary aim included fertility outcomes as a direct impact of chemotherapy, immunotherapy, or target therapy. Results We identified 75 patients who were treated with 28 unique contemporary oncologic agents. At least half of these agents demonstrated fertility inquiries in multiple patients referred. Agents with consultation &amp;gt;5 occasions included brentuximab (9), pembroluzimab (8), blinotumomab (8), pazopanib (6), and nivolumab (6). A total of 2,629 studies resulted from our search of which 56 studies met inclusion criteria determined by two independently blinded reviewers. Impact on fertility was defined as impaired spermatogenesis, reduced total sperm count/function, hypogonadism, impaired folliculogenesis or decreased ovarian reserve/function. Eight studies were conducted on animal models. Thirty-two studies reported an impact on fertility. Agents mostly commonly demonstrating fertility concerns included Melphalan (14), Ipilimumab (4), Pembrolizumab (3), Olaparib (2), and Trametinib (2). The most common drug classes affecting fertility outcomes included alkylating agents and immune checkpoint inhibitors. The majority of agents had only one study assessing fertility outcomes. At least a third of agents had literature to both support and oppose their impact on fertility. Conclusions Contemporary oncologic agents demonstrate significant variability in their impact on fertility. There is limited consensus on fertility outcomes amongst common oncologic agents referred to urologists for fertility workup. Evidence supporting negative fertility impacts is more commonly demonstrated among alkylating agents and immune checkpoint inhibitors. However, the available literature regarding the fertility impact of contemporary oncologic agents is limited and varied, reinforcing the need for provider familiarity and future research. Disclosure No.