Current Treatment Landscape Research Articles

Clinical characteristics and initial treatment patterns of patients with HCC in Korea: A multi-center real-world database analysis from the LINK research network.

e16116 Background: In Korea, liver cancer is the fifth most frequently diagnosed cancer and has the second highest cancer mortality rate. Despite recent advances in systemic therapy, patients with Hepatocellular carcinoma (HCC) continue to have poor prognoses as many are diagnosed at an advanced disease stage. To better understand the current treatment landscape and contribute to improved patient outcomes, the LINK (Liver Cancer in Korea) research network was established as a longitudinal real-world HCC database with annual data refresh. The aim was to provide current and up-to-date real-world insights into HCC patient characteristics, treatment patterns, and outcomes. Methods: LINK’s data sources are the electronic medical records of three leading academic hospitals (Asan Medical Center, Samsung Medical Center, Severance Hospital). Extracted data are standardized using a study-specific common data model to ensure comparability across hospitals. Adult patients with primary diagnosis of HCC (ICD-10: C22.0) in 2015-2020 were included and followed until death, loss to follow-up, or June 2021, whichever occurred first. Patients without valid treatment records or morphology codes or with other primary cancer diagnosis were excluded. Data on key patient and clinical characteristics, treatments, such as systemic anti-cancer therapy (SACT) regimens, and real-world outcomes were collected. Rule-based algorithms were developed to define initial treatments and lines of therapy in palliative SACT. Results: Of 25,480 HCC patients identified, 10,298 (40%) met eligibility criteria and were included in the analysis. The median age was 60 years and 19% were female. There were 74% of patients classified as Child-Pugh (CP) class A, 16% as B, 1% as C, and 9% with unknown CP at diagnosis. For albumin-bilirubin (ALBI) grade at diagnosis, 49% of patients were classified as grade 1, 45% as 2, 5% as 3, and 1% unknown. Loco-regional therapy was the most common initial treatment, with 54% and 13% of patients receiving transarterial therapy and local ablation therapy, respectively. A total of 628 patients (6%) undergone liver transplantation regardless of preceding treatments and 15% of patients were initially treated with hepatectomy. Only 2% received radiation therapy (RT) or RT in combination with cytotoxic chemotherapy as initial treatment. Among 3,026 patients who received SACT either as an initial (10%) or subsequent treatment, 67%, 20%, and 13% received 1 line, 2 lines, and 3 lines of therapy. The most common first-line SACT was sorafenib, followed by lenvatinib. Conclusions: The LINK database can serve as a multi-center research platform to facilitate fast and reliable real-world evidence generation for HCC patients. Future updates and subgroup analyses of interest can further evaluate the impact of new therapies and changes to HCC treatment guidelines in Korea.

Pancreatic Cancer: BRCA Targeted Therapy and Beyond.

Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related death in the US by 2030, despite accounting for only 5% of all cancer diagnoses. Germline gBRCA1/2-mutated PDAC represents a key subgroup with a favorable prognosis, due at least in part to additional approved and guideline-endorsed therapeutic options compared with an unselected PDAC cohort. The relatively recent incorporation of PARP inhibition into the treatment paradigm for such patients has resulted in renewed optimism for a biomarker-based approach to the management of this disease. However, gBRCA1/2 represents a small subgroup of patients with PDAC, and efforts to extend the indication for PARPi beyond BRCA1/2 mutations to patients with PDAC and other genomic alterations associated with deficient DNA damage repair (DDR) are ongoing, with several clinical trials underway. In addition, despite an array of approved therapeutic options for patients with BRCA1/2-associated PDAC, both primary and acquired resistance to platinum-based chemotherapies and PARPi presents a significant challenge in improving long-term outcomes. Herein, we review the current treatment landscape of PDAC for patients with BRCA1/2 and other DDR gene mutations, experimental approaches under investigation or in development, and future directions.

National Registries for Urothelial Cancer (UroNAT) and Prostate Cancer (ProNAT) by d-uo

The German Society of Uro-Oncologists ("Deutsche Uro-Onkologen e.V.", d-uo) provides a national registry for urothelial cancer (UroNat) and a national registry for prostate cancer (ProNAT). These registries aim to evaluate the standard of care for urothelial cancer of the bladder and the upper urinary tract as well as prostate cancer by office-based urologists, oncologists and outpatient hospital departments in Germany. This includes, but is not limited to, adherence to guidelines during the treatment of patients with urothelial cancer and prostate cancer. The registries aim to capture and analyse scientifically how patients with these two most frequent urological tumours are treated and how quality assurance is implemented to improve the quality of their outpatient treatment in Germany. Both registries may share basic patient data supplied by the non-interventional, prospective, multicentre VERSUS registry by d-uo, which has been ongoing since 2018 and today includes more than 15,000 patients with different urological malignancies. In the UroNAT and ProNAT registries, additional items and parameters are included to allow for more detailed analyses of outcomes of outpatient treatments in Germany, which have so far been unavailable from the German Cancer Registry. By documenting the current treatment landscape of urothelial and prostate cancer in the outpatient setting, the registries intend to identify potential improvements of patient care and to initiate their implementation into clinical practice. These non-interventional prospective registries only document daily routine diagnostics, clinical courses and procedures.

Infographic: The Current Treatment Landscape of Hereditary Angioedema

Infographic: The Current Treatment Landscape of Hereditary Angioedema

Management of Prostate Cancer in Older Adults.

The majority of men with prostate cancer are diagnosed when they are older than 65 years; however, clinical trial participants are disproportionately younger and more fit than the real-world population treated in typical clinical practices. It is, therefore, unknown whether the optimal approach to prostate cancer treatment is the same for older men as it is for younger and/or more fit men. Short screening tools can be used to efficiently assess frailty, functional status, life expectancy, and treatment toxicity risk. These risk assessment tools allow for targeted interventions to increase a patient's reserve and improve treatment tolerance, potentially allowing more men to experience the benefit of the significant recent treatment advances in prostate cancer. Treatment plans should also take into consideration each patient's individual goals and values considered within their overall health and social context to reduce barriers to care. In this review, we will discuss evidence-based risk assessment and decision tools for older men with prostate cancer, highlight intervention strategies to improve treatment tolerance, and contextualize these tools within the current treatment landscape for prostate cancer.

Artículo traducido] Necesidades clínicas no satisfechas y patrones de tratamiento de los pacientes pediátricos con psoriasis: estudio de evidencia en el mundo real en España

Background and objectiveReal-world evidence of paediatric psoriasis (PsO) is lacking in Spain. The purpose of this study was to identify physician-reported disease burden and current treatment patterns in a real-world paediatric PsO patient cohort in Spain. This will enhance our understanding of the disease and contribute to the development of regional guidelines. Material and methodThis retrospective analysis of a cross-sectional market research survey assessed the clinical unmet needs and treatment patterns in patients with paediatric PsO in Spain, as reported by their primary care and specialist physicians, using data collected as part of the Adelphi Real World Paediatric PsO Disease-Specific Program (DSP™) between February and October 2020. ResultsSurvey data from 57 treating physicians were included (71.9% [N = 41] dermatologists, 17.6% [N = 10] general practitioners/primary care physicians, and 10.5% [N = 6] paediatricians); the final analysis included 378 patients. At sampling, 84.1% (318/378) of patients had mild disease, 15.3% (58/378) had moderate disease and 0.5% (2/378) had severe disease. Retrospectively reported physician-judged severity at the time of PsO diagnosis recorded 41.8% (158/378) of patients with mild disease, 51.3% (194/378) with moderate disease and 6.9% (26/378) with severe disease. Overall, 89.3% (335/375) of patients were currently receiving topical PsO therapy, while 8.8% (33/375), 10.4% (39/375) and 14.9% (56/375) of patients were currently receiving phototherapy, conventional systemics and biologics, respectively. ConclusionsThese real-world data reflect the current burden and treatment landscape of paediatric PsO in Spain. The management of patients with paediatric PsO could be improved by further educating healthcare professionals and developing regional guidelines.

Narrative review on the role of immunotherapy in early triple negative breast cancer: unveiling opportunities and overcoming challenges.

Triple negative breast cancer (TNBC) represents a highly aggressive breast cancer subtype, historically managed with chemotherapy regimens predominantly involving anthracyclines and taxanes, yielding unfavorable prognoses. This review endeavors to offer a thorough examination of the present state of treatment strategies for early stage triple negative breast cancer (eTNBC), with a particular emphasis on immunotherapy modalities, combination therapies, predictive biomarkers, and ongoing clinical trials. The principal aim of this review is to meticulously assess the available literature, ascertain significant discoveries, and engage in discussions regarding their potential implications for future research endeavors, clinical applications, and policy formulation. This review was conducted using PubMed and Google Scholar databases, with the latest update performed in March 2023. The search strategy was designed to ensure a comprehensive analysis of the literature, with a focus on recent advancements. We critically assess the current eTNBC treatment landscape, covering efficacy and limitations of monotherapy, combination therapies, and predictive biomarkers. We highlight promising results from recent trials, address controversies surrounding chemotherapy, and explore optimal approaches for adjuvant and neoadjuvant therapy (NAT). Insights into personalized treatment strategies, ongoing trials, and future perspectives are provided, advancing our understanding of therapeutic options for eTNBC. Through a comprehensive analysis of the literature, this review highlights the potential of immunotherapy, particularly in combination with chemotherapy, as a promising approach for treating eTNBC. However, further research is warranted to optimize treatment strategies, refine patient selection criteria, and identify reliable biomarkers for predicting response to immune checkpoint inhibitors (ICIs). The findings of this review hold significant implications for future research, clinical practice, and policy-making, offering valuable insights into the current challenges and advancements in eTNBC treatment. Ultimately, this knowledge can contribute to improved patient outcomes, enhanced quality of life, and the development of more effective therapeutic approaches for eTNBC.

Characteristics of BAY 2599023 in the Current Treatment Landscape of Hemophilia A Gene Therapy.

Hemophilia A, a single gene disorder leading to deficient Factor VIII (FVIII), is a suitable candidate for gene therapy. The aspiration is for single administration of a genetic therapy that would allow the production of endogenous FVIII sufficient to restore hemostasis and other biological processes. This would potentially result in reliable protection from bleeding and its associated physical and emotional impacts. Gene therapy offers the possibility of a clinically relevant improvement in disease phenotype and transformational improvement in quality of life, including an opportunity to engage in physical activities more confidently. Gene therapy products for hemophilia A in advanced clinical development use adeno-associated viral (AAV) vectors and a codon-optimized B-domain deleted FVIII transgene. However, the different AAV-based gene therapies have distinct design features, such as choice of vector capsid, enhancer and promoter regions, FVIII transgene sequence and manufacturing processes. These, in turn, impact patient eligibility, safety and efficacy. Ideally, gene therapy technology for hemophilia A should offer bleed protection, durable FVIII expression, broad eligibility and limited response variability between patients, and long-term safety. However, several limitations and challenges must be overcome. Here, we introduce the characteristics of the BAY 2599023 (AAVhu37.hFVIIIco, DTX 201) gene therapy product, including the low prevalence in the general population of anti-AAV-hu37 antibodies, as well as other gene therapy AAV products and approaches. We will examine how these can potentially meet the challenges of gene therapy, with the ultimate aim of improving the lives of patients with hemophilia A.

DNA Supramolecular Hydrogel-Enabled Sustained Delivery of Metformin for Relieving Osteoarthritis.

Osteoarthritis (OA) is a musculoskeletal disorder affecting ∼500 million people worldwide. Metformin (MET), as an oral hypoglycemic drug approved by the Food and Drug Administration, has displayed promising potential for treating OA. Nonetheless, in the articular cavity, MET suffers from rapid clearance and cannot circumvent the severe inflammatory environment, greatly confining the therapeutic efficacy. Herein, DNA supramolecular hydrogel (DSH) has been utilized as a sustained drug delivery vehicle for MET to treat OA, which dramatically prolonged the retention time of MET in the articular cavity from 3 to 14 days and simultaneously exerted a greater anti-inflammatory effect. Our delivery platform, termed MET@DSH, better protects cartilage than single-agent MET. Additionally, the corresponding molecular mechanisms underlying the therapeutic effects were also analyzed. We anticipate this DNA supramolecular hydrogel-enabled sustained drug delivery and anti-inflammatory strategy will reshape the current landscape of OA treatment.

New Developments in the Treatment of Schizophrenia: An Expert Roundtable.

Schizophrenia is a disabling disorder that profoundly affects functioning and quality of life. While available antipsychotics have improved outcomes for patients with schizophrenia, they are relatively ineffective for negative and cognitive symptoms and are associated with a range of troublesome side effects. A significant unmet medical need for more effective and better-tolerated therapies remains. A roundtable consisting of 4 experts in the treatment of patients with schizophrenia convened to discuss the current treatment landscape, unmet needs from patient and societal perspectives, and the potential of emerging therapies with novel mechanisms of action (MOAs). Key areas of unmet need include optimal implementation of available treatments, effective treatment of negative and cognitive symptoms, improvements in medication adherence, novel MOAs, avoidance of postsynaptic dopamine blockade-related adverse effects, and individualized approaches to treatment. With the possible exception of clozapine, all currently available antipsychotics primarily act by blocking dopamine D2 receptors. Agents with novel MOAs are urgently needed to effectively target the full range of symptoms in schizophrenia and facilitate an individualized treatment approach. Discussion focused on promising novel MOAs that have demonstrated potential in phase 2 and 3 trials include muscarinic receptor agonism, trace amine-associated receptor 1 agonism, serotonin receptor antagonism/inverse agonism, and glutamatergic modulation. Results from early clinical trials of agents with novel MOAs are encouraging, particularly for muscarinic and trace amine-associated receptor 1 agonists. These agents offer renewed hope for meaningful improvement in the management of patients with schizophrenia.

Clinical Unmet Needs and Treatment Patterns of Paediatric Psoriasis Patients: A Real-World Evidence Study in Spain

Background and objectiveReal-world evidence of paediatric psoriasis (PsO) is lacking in Spain. The purpose of this study was to identify physician-reported disease burden and current treatment patterns in a real-world paediatric PsO patient cohort in Spain. This will enhance our understanding of the disease and contribute to the development of regional guidelines. Material and methodThis retrospective analysis of a cross-sectional market research survey assessed the clinical unmet needs and treatment patterns in patients with paediatric PsO in Spain, as reported by their primary care and specialist physicians, using data collected as part of the Adelphi Real World Paediatric PsO Disease-Specific Program (DSP™) between February and October 2020. ResultsSurvey data from 57 treating physicians were included (71.9% [N=41] dermatologists, 17.6% [N=10] general practitioners/primary care physicians, and 10.5% [N=6] paediatricians); the final analysis included 378 patients. At sampling, 84.1% (318/378) of patients had mild disease, 15.3% (58/378) had moderate disease and 0.5% (2/378) had severe disease. Retrospectively reported physician-judged severity at the time of PsO diagnosis recorded 41.8% (158/378) of patients with mild disease, 51.3% (194/378) with moderate disease and 6.9% (26/378) with severe disease. Overall, 89.3% (335/375) of patients were currently receiving topical PsO therapy, while 8.8% (33/375), 10.4% (39/375) and 14.9% (56/375) of patients were currently receiving phototherapy, conventional systemics and biologics, respectively. ConclusionsThese real-world data reflect the current burden and treatment landscape of paediatric PsO in Spain. The management of patients with paediatric PsO could be improved by further educating healthcare professionals and developing regional guidelines.

Molecularly Targeted Therapy in Acute Myeloid Leukemia: Current Treatment Landscape and Mechanisms of Response and Resistance.

Treatment for acute myeloid leukemia (AML) has evolved rapidly over the last decade as improved understanding of cytogenetic and molecular drivers of leukemogenesis refined survival prognostication and enabled development of targeted therapeutics. Molecularly targeted therapies are now approved for the treatment of FLT3 and IDH1/2-mutated AML and additional molecularly and cellularly targeted therapeutics are in development for defined patient subgroups. Alongside these welcome therapeutic advancements, increased understanding of leukemic biology and treatment resistance has resulted in clinical trials investigating combinations of cytotoxic, cellular, and molecularly targeted therapeutics resulting in improved response and survival outcomes in patients with AML. Herein, we comprehensively review the current landscape of IDH and FLT3 inhibitors in clinical practice for the treatment of AML, highlight known resistance mechanisms, and discuss new cellular or molecularly targeted therapies currently under investigation in ongoing early phase clinical trials.

Abstract P2-01-01: Interim analysis (n=200) from ELEANOR: a multi-national, prospective, non-interventional study among patients with HER2+ and HR+ early breast cancer treated with extended adjuvant neratinib in the clinical routine

Abstract Background Recent advances in the treatment of human epidermal growth factor receptor positive (HER2+) early breast cancer (eBC) have led to a reduction in recurrence risk; still a relevant percentage of patients relapses over time, predominantly presenting with distant recurrence. Neratinib is registered in Europe as extended adjuvant treatment for adult patients with HER2+, hormone receptor positive (HR+) eBC, who completed adjuvant trastuzumab-based therapy within one year prior to start of neratinib. In the ExteNET study, neratinib improved the absolute 5-year invasive disease-free survival (iDFS) rate by 5.1% versus placebo in this population (90.8% vs. 85.7%; HR 0.58 [95% CI 0.41-0.82]), mainly by reducing the rate of distant metastases. According to explorative analyses from ExteNET, the effect may be even more pronounced in patients with non-pCR after neoadjuvant trastuzumab treatment and/or in patients completing the full duration of neratinib therapy (i.e. ≥11 months of neratinib treatment). Diarrhea, the most common grade 3 adverse event (neratinib: 39% without primary diarrhea prophylaxis, median cumulative duration 5 days; placebo: 1%; no grade 4 events) can generally be managed through adequate prophylaxis and treatment management. ELEANOR is the first non-interventional study (NIS) of real-world use of neratinib and its management in eBC patients in Germany, Austria and Switzerland. Methods Enrollment of 300 adult female patients with HER2+/HR+ eBC is planned in accordance with the SmPC specifications. Primary endpoint is the rate of patients adherent to neratinib treatment (i.e. neratinib use for ≥75% of treatment days). Secondary objectives include characterization of patients scheduled to receive neratinib, details on neratinib treatment, recurrences, safety/tolerability, and health-related quality of life (HRQoL). CANKADO, an eHealth application developed to support patient/physician communication, is an integral part of the NIS. Here, we report results of the preplanned interim analysis based on 200 enrolled patients. Results At data cut-off (May 2022), 202 patients had been observed for 3 months; patient enrollment is ongoing. Median age was 53.0 years and 66.3% of patients were at increased risk of disease recurrence (defined as non-pCR or AJCC stage > I). Most patients had received prior neoadjuvant treatment (79.7%). Post-neoadjuvant treatment included dual HER2 blockade with trastuzumab and pertuzumab (38.8%/23.9% of pCR/non-pCR patients) and trastuzumab-emtansine (T-DM1, 53.5% of non-pCR patients). Neratinib treatment had been documented for 187 patients, treatment was ongoing for 46.0% of patients. Diarrhea was the most common adverse event (78.6% any grade, 19.3% grade 3, 2 patients grade 4), but was markedly lower when indirectly compared to ExteNET (39% grade 3). The neratinib dose escalation schedule was chosen for 36.4% of patients and led to a decreased incidence of severe diarrhea (16.2% grade 3, no grade 4 events). 93.9% (95% CI: 87.9-97.5%) of 115 evaluable patients adhered to neratinib treatment. Conclusion The results of this preplanned interim analysis reflect the current treatment landscape in Germany, Austria and Switzerland. These results confirm, in line with the observed adherence data, that extended adjuvant neratinib use is feasible in typical clinical practice settings. Furthermore, treatment management strategies such as diarrhea prophylaxis or neratinib dose escalation are routinely used and can increase treatment tolerability markedly. The study is funded by Pierre Fabre Pharma GmbH (Freiburg, Germany), Pierre Fabre Pharma Austria (Wels, Austria) and Pierre Fabre Pharma AG (Allschwil, Switzerland). Citation Format: Rupert Bartsch, Nadia Harbeck, Denise Wrobel, Matthias Zaiss, Jürgen Terhaag, Dagmar Guth, Andrea Distelrath, Rachel Wuerstlein, Mark-Oliver Zahn, Diana Lüftner, Michael Schwitter, Marija Balic, Christian Jackisch, Volkmar Müller, Gabriel Rinnerthaler, Marcus Schmidt, Khalil Zaman, Timo Schinköthe, Anna Resch, Urs Breitenstein. Interim analysis (n=200) from ELEANOR: a multi-national, prospective, non-interventional study among patients with HER2+ and HR+ early breast cancer treated with extended adjuvant neratinib in the clinical routine [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-01-01.

Impact of cytoreductive nephrectomy (CRN) on overall survival (OS) in metastatic non–clear cell renal cancer (nccRCC).

730 Background: Non-clear cell renal cell carcinoma (nccRCC) accounts for 25% of kidney cancer diagnoses and encompasses a diverse group of kidney tumors with distinct biology for which treatment in the metastatic setting is evolving. The role of CRN for nccRCC population in the current treatment landscape remains unclear. Methods: We retrospectively identified patients (pts) with nccRCC from The National Cancer Database (NCDB) participant user file (PUF) for Kidney and Renal Pelvis Tumors. Pts with de novo metastatic disease diagnosed between 2006 and 2017, received systemic treatment (trt) with immunotherapy (IO) or non-immunotherapy (NIO) and either underwent or could have undergone a CRN were selected. Demographic and disease characteristics were summarized using descriptive statistics. The cumulative incidence of CRN with death without CRN as a competing risk, was estimated using the Nelson-Aalen estimator. The association of each demographic and disease characteristic on the cumulative incidence of CRN was evaluated using univariate Fine-Gray regression. The effect of CRN on survival was visualized using a Simon-Makuch plot. P values were based on Mantel-Byar test. Cox regression with a time-dependent predictor was used to estimate the change in the hazard of death after CRN. Results: We identified 3644 pts, 72% male, mean age 61 ±13 years. Nearly 40% of pts (n=1453) had sarcomatoid histology, followed by 30% with papillary (n=1075). Most pts, 96% (n=3489) received NIO systemic trt and only 9% were treated with IO (n=319). Nearly half of the study population (45%) underwent CRN (n=1642). Of these, 95% received NIO trt (n=1564) and 9% received IO (n=152). Pts who underwent CRN were younger and less likely to have bone, brain or liver metastases. Minority pts were less likely to undergo CRN. Mean time from dx to surgery was 1.1 ±1.7 months. For all pts, mOS was 9 months (95% CI: 8.6-9.4). OS was improved for pts who underwent CRN vs those who did not (11.3 vs 7.5 months, p<0.0001). In multivariate analysis, cytoreductive nephrectomy was associated with a reduction in the risk of death, HR 0.73 (95% CI: 0.68, 0.80, p<.0001). Conclusions: For pts with de novo metastatic nccRCC, CRN is associated with improved outcomes. Further analysis regarding the effect of treatment regimens on survival outcomes is warranted and planned. Prospective randomized trials in the modern treatment era are needed to further assess the timing and impact of CRN on outcomes in pts with metastatic nccRCC. [Table: see text]

Current Treatment Landscape for Early Triple-Negative Breast Cancer (TNBC)

Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers and is characterized by an aggressive nature and a high rate of recurrence despite neoadjuvant and adjuvant chemotherapy. Although novel agents are constantly being introduced for the treatment of breast cancer, conventional cytotoxic chemotherapy based on anthracyclines and taxanes is the mainstay treatment option for TNBC. Based on CTNeoBC pooled analysis data, the achievement of pathologic CR (pCR) in TNBC is directly linked to improved survival outcomes. Therefore, the treatment paradigm for early TNBC has shifted to neoadjuvant treatment, and the escalation of neoadjuvant chemotherapy to improve the pCR rate and the addition of post-neoadjuvant chemotherapy to control the residual disease have been investigated. In this article, we review the current treatment landscape for early TNBC, from standard cytotoxic chemotherapy to recent data on immune checkpoint inhibitors, capecitabine, and olaparib.

Peyronie's Disease: An Outcomes-Based Guide to Non-Surgical and Novel Treatment Modalities.

The clinical landscape of Peyronie's disease is everchanging. There has been growing interest in non-invasive therapeutic options that could assist patients with achieving a meaningful reduction in penile curvature without surgical intervention. These therapies are wide-ranging in terms of their mechanisms of action, efficacies, and short- and long-term safety profiles. Recently, an abundance of outcomes literature on longstanding and novel non-surgical treatment modalities has been published. For sexual medicine providers hoping to offer patients the most up-to-date and evidence-based treatments for the management of Peyronie's disease, it can be challenging to gain a thorough understanding of this body of literature. In this clinical management review, the workup and current theories on the pathophysiology of Peyronie's disease are reviewed, and the most recent outcomes data on the currently available non-surgical treatment modalities are presented. With an accurate understanding of the current landscape of Peyronie's disease treatment, sexual health providers will be able to better evaluate and engage in evidence-based shared decision-making with their patients.

The Efficacy of Using Patient-Derived Organoids to Predict Treatment Response in Colorectal Cancer.

Colorectal cancer is an important cause of morbidity and mortality worldwide. The current treatment landscape includes chemotherapy, targeted therapy, immunotherapy, radiotherapy, and surgery. A key challenge to improving patient outcomes is the significant inter-patient heterogeneity in treatment response. Tumour organoids derived from the patients' tumours via surgically resected or endoscopically biopsied tissue, have emerged as promising models for personalised medicine. This review synthesises the findings, to date, of studies which have explored the efficacy of ex vivo organoid sensitivity testing for predicting treatment response. Most studies have focused on predicting the response to standard-of-care radiotherapy and chemotherapy options. There is strong evidence to support organoid sensitivity testing of ionising radiation, 5-fluorouracil, and irinotecan, and to a lesser extent, oxaliplatin and TAS-102. Fewer studies have used organoids to identify patients who are likely to benefit from novel treatment options that otherwise remain in clinical trials. This review also summarises recent advancements in organoid culture to include non-epithelial components of the tumour microenvironment, to allow testing of immunotherapy and certain targeted therapy options. Overall, further prospective trials will support the implementation of organoid-based personalised medicine for colorectal cancer patients in the future.

Current and Future Landscape of Perioperative Treatment for Muscle-Invasive Bladder Cancer.

Cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy is the current standard of care for muscle-invasive bladder cancer (MIBC). However, less than half of patients are candidates for this treatment, and 50% will develop metastatic disease. Adjuvant chemotherapy could be offered if neoadjuvant treatment has not been administered for suitable patients. It is important to reduce the risk of systemic recurrence and improve the prognosis of localized MIBC. Systemic therapy for metastatic urothelial carcinoma has evolved in recent years. Immune checkpoint inhibitors and targeted agents, such as antibody-drug conjugates or FGFR inhibitors, are new therapeutic alternatives and have shown their benefit in advanced disease. Currently, several clinical trials are investigating the role of these drugs, as monotherapy and in combination with chemotherapy, in the neoadjuvant and adjuvant settings with promising outcomes. In addition, the development of predictive biomarkers could predict responses to neoadjuvant therapies.

Pharmacological management of type 2 diabetes: clinical considerations and future perspectives

The management of type 2 diabetes continues to evolve with the historical glucocentric nature of care, paving the way toward more holistic and comorbidity-based management largely due to the advent of newer medications and trial data. Clinicians need to be aware that an understanding of not only the current treatment landscape but also the future developments in care and therapy is required in order to understand the best options for the management of their patients. This article will discuss current perspectives in the pharmacological management of type 2 diabetes, largely focusing on recent trial developments and associated future trials and molecules that may impact type 2 diabetes care in the near future.

Zolbetuximab: An Investigational First-Line Treatment for CLDN18.2-positive, HER2-negative Gastric and Gastro-oesophageal Junction Cancer

Biomarker-based targeted therapies have changed the cancer treatment paradigm. While early-stage gastric and gastro-oesophageal junction (GOJ) adenocarcinomas can benefit from surgery, advanced presentations of these diseases have limited therapeutic options and poor prognoses. Zolbetuximab, a chimeric monoclonal antibody targeting Claudin 18.2 (CLDN18.2), exerts its effect through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. It has emerged as a promising treatment for advanced gastric/GOJ cancer. Clinical trials have assessed its efficacy and safety across multiple phases, demonstrating significant improvements in progression-free survival and overall survival. The safety profile of zolbetuximab primarily includes manageable gastrointestinal adverse events, namely nausea and vomiting. Zolbetuximab's potential extends beyond its primary indication, with on-going trials exploring its efficacy in other CLDN18.2-expressing malignancies, such as pancreatic adenocarcinoma. This review highlights zolbetuximab's potential as a first-line therapy for CLDN18.2-positive, HER2-negative gastric and GOJ adenocarcinomas, shedding light on its mechanism of action, clinical trial results, safety profile and current treatment landscape.