{"title":"Steroid Premedication and Monoclonal Antibody Therapy: Should We Reconsider?","authors":"Emma-Anne Karlsen, Euan Walpole, Fiona Simpson","doi":"10.1007/s11864-023-01170-4","DOIUrl":"10.1007/s11864-023-01170-4","url":null,"abstract":"<p><strong>Opinion statement: </strong>Monoclonal antibody (mAb) therapy is now considered a main component of cancer therapy in Australia. Although traditionally thought of as pure signalling inhibitors, a large proponent of these medications function through antibody-dependent cell-mediated cytotoxicity (ADCC). Currently, most protocols and institutional guidelines for ADCC-mediated mAbs promote the use of corticosteroids as premedication: this is implemented to reduce infusion-related reactions (IRRs) and antiemesis prophylaxis and combat concurrently administered chemotherapy-related syndromes. Concerningly, the inhibitory effects of ADCC by corticosteroids are well documented; henceforth, it is possible the current standard of care is misaligned to the literature surrounding ADCC. Subsequently, clinicians' decisions to act in contrast to this literature may be reducing the efficacy of mAbs. The literature suggests that the redundant use of corticosteroids should be cautioned against when used in conjunction with ADCC-mediated mAbs-this is due to the consequent reduction in anti-tumour activity. Owing to the fact IRRs typically occur upon initial infusion, the authors advocate for individual clinicians and institutional protocols to considering augmenting their practice to corticosteroid premedication at the first dose only, unless clinically indicated. Additionally, product information (PI) and consumer medicine information (CMI) documents distributed by Australian and international regulatory agencies should consider disclosing the risk of concurrent steroids with these medications. Moreover, the authors suggest considering alternative medications for the management of side effects.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":" ","pages":"275-283"},"PeriodicalIF":4.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10894762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Treatment of node-positive endometrial cancer: chemotherapy, radiation, immunotherapy, and targeted therapy.","authors":"Elizabeth A Tubridy, Neil K Taunk, Emily M Ko","doi":"10.1007/s11864-023-01169-x","DOIUrl":"10.1007/s11864-023-01169-x","url":null,"abstract":"<p><strong>Opinion statement: </strong>The standard of treatment for node-positive endometrial cancer (FIGO Stage IIIC) in North America has been systemic therapy with or without additional external beam radiation therapy (RT) given as pelvic or extended field RT. However, this treatment paradigm is rapidly evolving with improvements in systemic chemotherapy, the emergence of targeted therapies, and improved molecular characterization of these tumors. The biggest question facing providers regarding management of stage IIIC endometrial cancer at this time is: what is the best management strategy to use with regard to combinations of cytotoxic chemotherapy, immunotherapy, other targeted therapeutics, and radiation that will maximize clinical benefit and minimize toxicities for the best patient outcomes? While clinicians await the results of ongoing clinical trials regarding combined immunotherapy/RT as well as management based on molecular classification, we must make decisions regarding the best treatment combinations for our patients. Based on the available literature, we are offering stage IIIC patients without measurable disease postoperatively both adjuvant chemotherapy and IMRT with carboplatin, paclitaxel, and with or without pembrolizumab/dostarlimab as primary adjuvant therapy. Patients with measurable disease post operatively, high risk histologies, or stage IV disease receive chemoimmunotherapy, and vaginal brachytherapy is added for those with uterine risk factors for vaginal recurrence. In the setting of endometrioid EC recurrence more than 6 months after treatment, patients with pelvic nodal and vaginal recurrence are offered IMRT and brachytherapy without chemotherapy. For measurable recurrence not suitable for pelvic radiation alone, chemoimmunotherapy is preferred as standard of care.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":" ","pages":"330-345"},"PeriodicalIF":4.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10894756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting BRCA and PALB2 in Pancreatic Cancer.","authors":"Sriram Anbil, Kim A Reiss","doi":"10.1007/s11864-023-01174-0","DOIUrl":"10.1007/s11864-023-01174-0","url":null,"abstract":"<p><strong>Opinion statement: </strong>An important subgroup of pancreatic ductal adenocarcinomas (PDACs) harbor pathogenic variants in BRCA1, BRCA2, or PALB2. These tumors are exquisitely sensitive to platinum-based chemotherapy and patients may experience deep and durable responses to this treatment. PARP inhibitors offer potential respite from the cumulative toxicities of chemotherapy as they significantly extend progression-free survival compared to a chemotherapy holiday. Given the lack of proven survival benefit, the decision to use a maintenance PARP inhibitor rather than continue chemotherapy should be individualized. Interestingly, in both published clinical trials of maintenance PARP inhibitors, there is a striking range of interpatient benefit: Even in the platinum-sensitive setting, roughly 25% of tumors appear to be PARP inhibitor refractory (progressive disease within 2 months of starting treatment), 50% sustain moderate benefit (up to 2 years), and 25% are hyper-responsive (more than 2 years of benefit). This finding highlights the need to refine our understanding of which patients will respond to maintenance PARP inhibitors, both by being able to identify biallelic loss and by deepening our knowledge of resistance mechanisms and who develops them. Recent data supports that reversion mutations are common in PARP inhibitor refractory patients, but we have little understanding of the mechanisms that drive delayed resistance and long-term responses. Identifying which patients are more prone to certain mechanisms of resistance and tackling them with specific treatment strategies are areas of active investigation. Additionally, given that PARP inhibitors have limited overall efficacy for most patients, upfront combination strategies are an important future strategy.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":" ","pages":"346-363"},"PeriodicalIF":4.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139681852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"One Size Fits Some: Approaching Rare Malignancies of the Urinary Tract","authors":"","doi":"10.1007/s11864-024-01187-3","DOIUrl":"https://doi.org/10.1007/s11864-024-01187-3","url":null,"abstract":"<h3>Opinion Statement</h3> <p>Urothelial carcinoma is the predominant cancer of the urinary tract but when divergent and subtype histology (non-urothelial) are identified at time of pathologic diagnosis, therapeutic and diagnostic challenges transpire. To this end, pathologic review to confirm any non-urothelial histology is key since these subtypes can often be overlooked. Few prospective trials are dedicated to understanding these non-urothelial histologic types; however, current, and past trials did allow patients with these non-urothelial histologic types to enroll, and inferences can be made about treatment efficacy and survival. Existing treatment regimens for non-urothelial bladder cancers are akin to standard urothelial cancer regimens using surgical approaches for localized disease and platinum-based chemotherapy for advanced disease. The reported clinical trials, that will be discussed, center on non-urothelial histologic types. These studies, albeit limited, provide critical insight into tumor biology and response to standard platinum-based chemotherapy, immune checkpoint inhibitors, and antibody drug conjugates. The inclusion of non-urothelial histologic types will be essential for clinical trials in development to provide further therapeutic advances and provide essential efficacy data.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":"73 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139690347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Desmoid Tumors: Current Perspective and Treatment.","authors":"Ankit Mangla, Nikki Agarwal, Gary Schwartz","doi":"10.1007/s11864-024-01177-5","DOIUrl":"10.1007/s11864-024-01177-5","url":null,"abstract":"<p><strong>Opinion statement: </strong>Desmoid tumors are rare tumors with a tendency to infiltrate locally. The lack of a standard treatment approach makes choosing the most appropriate treatment for patients challenging. Most experts recommend watchful observation for asymptomatic patients as spontaneous regression of tumor is observed in up to 20% of patients. Upfront resection of the desmoid tumor has fallen out of favor due to high morbidity and high relapse rates associated with the tumor. Systemic therapy has evolved over several decades. Where chemotherapy, hormonal therapy, and non-steroidal anti-inflammatory drugs were used over the last several decades, tyrosine kinase inhibitors came to the forefront within the last decade. Most recently, gamma-secretase inhibitors have shown significant clinical benefit in patients with desmoid tumors, bringing forth an entirely new mechanistic approach. Several Wnt pathway inhibitors are also under development. Invasive approaches like cryoablation have also shown clinical benefit in patients with extra-abdominal desmoid tumors in recent years. The recent approval of nirogacestat has ushered in a new era of treatment for patients diagnosed with desmoid tumors. Several new molecules are expected to be approved over the coming years.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":" ","pages":"161-175"},"PeriodicalIF":4.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10873447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Research Progress on the Use of Metformin in Leukemia Treatment.","authors":"Qian Wang, Xudong Wei","doi":"10.1007/s11864-024-01179-3","DOIUrl":"10.1007/s11864-024-01179-3","url":null,"abstract":"<p><strong>Opinion statement: </strong>Metformin is a first-line drug in the clinical treatment of type 2 diabetes. Its main molecular mechanism involves the activation of adenosine 5'-monophosphate-activated protein kinase (AMPK), which regulates cell energy metabolism. Many clinical studies have shown that metformin can reduce the incidence and mortality of cancer in patients with or without diabetes. In vitro studies also confirmed that metformin can inhibit proliferation, promote apoptosis, and enhance the response of cells to chemical drugs and other anticancer effects on a variety of leukemia cells. In recent years, leukemia has become one of the most common malignant diseases. Although great progress has been made in therapeutic approaches for leukemia, novel drugs and better treatments are still needed to improve the therapeutic efficacy of these treatments. This article reviews the application status and possible mechanism of metformin in the treatment of leukemia to further understand the anticancer mechanism of metformin and expand its clinical application.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":" ","pages":"220-236"},"PeriodicalIF":4.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10873432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David Gritsch, Sandro Santagata, Priscilla K Brastianos
{"title":"Integrating Systemic Therapies into the Multimodality Therapy of Patients with Craniopharyngioma.","authors":"David Gritsch, Sandro Santagata, Priscilla K Brastianos","doi":"10.1007/s11864-023-01156-2","DOIUrl":"10.1007/s11864-023-01156-2","url":null,"abstract":"<p><strong>Opinion statement: </strong>The integration of targeted therapy into the multimodal management of craniopharyngiomas represents a significant advancement in the field of neuro-oncology. Historically, the management of these tumors has been challenging due to their proximity to vital brain structures, necessitating a delicate balance between tumor control and the preservation of neurological function. Traditional treatment modalities, such as surgical resection and radiation, while effective, carry their own set of risks, including potential damage to surrounding healthy tissues and the potential for long-term side effects. Recent insights into the molecular biology of craniopharyngiomas, particularly the discovery of the BRAF V600E mutation in nearly all papillary craniopharyngiomas, have paved the way for a targeted systemic treatment approach. However, advances have been limited for adamantinomatous craniopharyngiomas. The success of BRAF/MEK inhibitors in clinical trials underscores the potential of these targeted therapies not only to control tumor growth but also to reduce the need for more invasive treatments, potentially minimizing treatment-related complications. However, the introduction of these novel therapies also brings forth new challenges, such as determining the optimal timing, sequencing, and duration of targeted treatments. Furthermore, there are open questions regarding which specific BRAF/MEK inhibitors to use, the potential need for combination therapy, and the strategies for managing intolerable adverse events. Finally, ensuring equitable access to these therapies, especially in healthcare systems with limited resources, is crucial to prevent widening healthcare disparities. In conclusion, targeted therapy with BRAF/MEK inhibitors holds great promise for improving outcomes and quality of life for patients with BRAF-mutated craniopharyngiomas. However, additional research is needed to address the questions that remain about its optimal use and integration into comprehensive treatment plans.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":" ","pages":"261-273"},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11203386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139652015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rita Khoury, Tarek Assi, Rebecca Ibrahim, Tony Ibrahim, Benjamin Verret, Clemence Henon, Ratislav Bahleda, Axel Le Cesne
{"title":"A Comprehensive Review on the Role of Lurbinectedin in Soft Tissue Sarcomas.","authors":"Rita Khoury, Tarek Assi, Rebecca Ibrahim, Tony Ibrahim, Benjamin Verret, Clemence Henon, Ratislav Bahleda, Axel Le Cesne","doi":"10.1007/s11864-024-01178-4","DOIUrl":"10.1007/s11864-024-01178-4","url":null,"abstract":"<p><strong>Opinion statement: </strong>Soft tissue sarcoma (STS), a substantial group of aggressive and rare tumors with tissue heterogeneity, is infrequently represented in clinical trials with an urgent necessity for newer treatment options. Lurbinectedin, an analog of trabectedin, is currently approved, in various countries, as a single agent, for the treatment of patients with relapsed small cell lung cancer (SCLC). However, preclinical and phase I and phase II trials have demonstrated the efficacy of lurbinectedin in different tumor types, including STS. The better understanding of the pathophysiology and evolution of STS as well as the mechanism of action of lurbinectedin in addition to the available data regarding the activity of this drug in this subset of patients will pave the way to newer therapeutic options and strategies.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":" ","pages":"176-190"},"PeriodicalIF":4.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139698819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adam B Weiner, Raag Agrawal, Luca F Valle, Ida Sonni, Amar U Kishan, Matthew B Rettig, Steven S Raman, Jeremie Calais, Paul C Boutros, Robert E Reiter
{"title":"Impact of PSMA PET on Prostate Cancer Management.","authors":"Adam B Weiner, Raag Agrawal, Luca F Valle, Ida Sonni, Amar U Kishan, Matthew B Rettig, Steven S Raman, Jeremie Calais, Paul C Boutros, Robert E Reiter","doi":"10.1007/s11864-024-01181-9","DOIUrl":"10.1007/s11864-024-01181-9","url":null,"abstract":"<p><strong>Opinion statement: </strong>PSMA-PET has been a practice-changing imaging biomarker for the management of men with PCa. Research suggests improved accuracy over conventional imaging and other PET radiotracers in many contexts. With multiple approved PSMA-targeting radiotracers, PSMA PET will become even more available in clinical practice. Its increased use requires an understanding of the prospective data available and caution when extrapolating from prior trial data that utilized other imaging modalities. Future trials leveraging PSMA PET for treatment optimization and management decision-making will ultimately drive its clinical utility.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":" ","pages":"191-205"},"PeriodicalIF":4.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11034977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rubina Ratnaparkhi, Melissa Javellana, Andrea Jewell, Lori Spoozak
{"title":"Evaluation of Homologous Recombination Deficiency in Ovarian Cancer.","authors":"Rubina Ratnaparkhi, Melissa Javellana, Andrea Jewell, Lori Spoozak","doi":"10.1007/s11864-024-01176-6","DOIUrl":"10.1007/s11864-024-01176-6","url":null,"abstract":"<p><strong>Opinion statement: </strong>Homologous recombination deficiency (HRD) is an important biomarker guiding selection of ovarian cancer patients who will derive the most benefit from poly(ADP-ribose) polymerase inhibitors (PARPi). HRD prevents cells from repairing double-stranded DNA damage with high fidelity, PARPis limit single-stranded repair, and together these deficits induce synthetic lethality. Germline or somatic BRCA mutations represent the narrowest definition of HRD, but do not reflect all patients who will have a durable PARPi response. HRD can also be defined by its downstream consequences, which are measured by different metrics depending on the test used. Ideally, all patients will undergo genetic counseling and germline testing shortly after diagnosis and have somatic testing sent once an adequate tumor sample is available. Should barriers to one test be higher, pursuing germline testing with reflex to somatic testing for BRCA wildtype patients or somatic testing first strategies are both evidence-based. Ultimately both tests offer complementary information, germline testing should be pursued for any patient with a history of ovarian cancer, and somatic testing is valuable at recurrence if not performed in the upfront setting. There is a paucity of data to suggest superiority of one germline or somatic assay; therefore, selection should optimize turnaround time, cost to patients, preferred result format, and logistical burden. Each clinic should implement a standard testing strategy for all ovarian cancer patients that ensures HRD status is known at the time of upfront chemotherapy completion to facilitate comprehensive counseling about anticipated maintenance PARPi benefit.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":" ","pages":"237-260"},"PeriodicalIF":4.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139652014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}