The evolving posology and administration of immune checkpoint inhibitors: subcutaneous formulations.

Immune checkpoint inhibitors (ICIs) have transformed cancer care. Recently, atezolizumab gained its first global approval in a subcutaneous (SC) formulation by the UK medicines regulator, being notable as the first time an FDA- and/or European Medicines Agency (EMA)-approved ICI has been licensed via this administration route. Here, we discuss this approval, other SC ICIs in development, and the benefits and challenges of this administration route, including potential implications for patient care.

A remnant never forgotten: the utility of circulating tumor DNA in treatment guidance of urachal cancer.

Urachal cancer is a rare malignancy of the urachus that is treated with surgical resection if localized and systemic chemotherapy for metastatic disease. Circulating tumor DNA (ctDNA) is a single-stranded or double-stranded DNA released by tumor cells into the blood and harbored the mutations of the original tumor, shedding new light on molecular diagnosis and monitoring of cancer. We report a case of resected localized urachal cancer with clear surgical margins and negative lymph node dissection but elevated ctDNA that progressed to metastatic disease. We also highlight the possibility of using ctDNA levels to assist in adjuvant therapy.

Cost effectiveness of immunotherapy combination therapies for endometrial cancer.

Over the past five years (2019-2023), several new targeted therapies and immunotherapy has been approved in treating relapsed cervical, ovarian, and endometrial cancers. Concurrently, there has been growing recognition of financial toxicity associated with cancer care during this time period. As such, we reviewed FDA approvals from 2019 to 2013 and identified the following approvals in gynecologic oncology: pembrolizumab plus lenvatinib, pembrolizumab for recurrent endometrial cancer that is MSI-H/dMMR, tisotumab vedotin, dostarlimab as single-agent therapy, and dostarlimab plus chemotherapy. We focused on approvals for endometrial cancer, and conducted a cost-effectiveness analysis for combination options approved in treating recurrent or advanced endometrial cancer (i.e. pembrolizumab plus lenvatinib versus placebo; dostarlimab plus chemotherapy versus placebo), and found neither regimen was cost-effective at a willingness-to-pay of $100,000 per Equal Value of Life Years Gained (evLYG). While these costs may not necessarily be translated to an individual patient, these costs are absorbed by healthcare systems and insurance providers on a larger scale with downstream effects on individuals contributing to healthcare costs a whole.

Supplement Use and Increased Risks of Cancer: Unveiling the Other Side of the Coin.

There is a rising trend in the consumption of dietary supplements, especially among adults, with the purpose of improving health. While marketing campaigns tout the potential health benefits of using dietary supplements, it is critical to evaluate the potential harmful effects associated with these supplements as well. The majority of the scarce research on the potential harmful effects of vitamins focuses on the acute or chronic toxicities associated with the use of dietary supplements. Quality research is still required to further investigate the risks of long-term use of dietary supplements, especially the risk of developing cancers. The present review concentrates on studies that have investigated the association between the risk of developing cancers and associated mortality with the risk of dietary supplements. Such an association has been reported for several vitamins, minerals, and other dietary supplements. Even though several of these studies come with their own shortcomings and critics, they must draw attention to further investigate long-term adverse effects of dietary supplements and advise consumers and healthcare providers to ponder the extensive use of dietary supplements.

Cardiovascular/anti-inflammatory drugs repurposed for treating or preventing cancer: A systematic review and meta-analysis of randomized trials.

BACKGROUND: Due to encouraging pre-clinical data and supportive observational studies, there has been growing interest in applying cardiovascular drugs (including aspirin, angiotensin-converting enzyme [ACE] inhibitors, statins, and metformin) approved to treat diseases such as hypertension, hyperlipidemia, and diabetes mellitus to the field of oncology. Moreover, given growing costs with cancer care, these medications have offered a potentially more affordable avenue to treat or prevent recurrence of cancer. We sought to investigate the anti-cancer effects of drugs repurposed from cardiology or anti-inflammatories to treat cancer. We specifically evaluated the following drug classes: HMG-CoA reductase inhibitors (statins), cyclo-oxygenase inhibitors, aspirin, metformin, and both angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors. We also included non-steroidal anti-inflammatory drugs (NSAIDs) because they exert a similar mechanism to aspirin by blocking prostaglandins and reducing inflammation that is thought to promote the development of cancer. METHODS: We performed a systematic literature review using PubMed and Web of Science with search terms including "aspirin," "NSAID," "statin" (including specific statin drug names), "metformin," "ACE inhibitors," and "ARBs" (including specific anti-hypertensive drug names) in combination with "cancer." Searches were limited to human studies published between 2000 and 2023. MAIN OUTCOMES AND MEASURES: The number and percentage of studies reported positive results and pooled estimates of overall survival, progression-free survival, response, and disease-free survival. RESULTS: We reviewed 3094 titles and included 67 randomized clinical trials. The most common drugs that were tested were metformin (n = 21; 30.9%), celecoxib (n = 20; 29.4%), and simvastatin (n = 8; 11.8%). There was only one study that tested cardiac glycosides and none that studied ACE inhibitors. The most common tumor types were non-small-cell lung cancer (n = 19; 27.9%); breast (n = 8; 20.6%), colorectal (n = 7; 10.3%), and hepatocellular (n = 6; 8.8%). Most studies were conducted in a phase II trial (n = 38; 55.9%). Most studies were tested in metastatic cancers (n = 49; 72.1%) and in the first-line setting (n = 36; 521.9%). Four studies (5.9%) were stopped early because of difficulty with accrual. The majority of studies did not demonstrate an improvement in either progression-free survival (86.1% of studies testing progression-free survival) or in overall survival (94.3% of studies testing overall survival). Progression-free survival was improved in five studies (7.4%), and overall survival was improved in three studies (4.4%). Overall survival was significantly worse in two studies (3.8% of studies testing overall survival), and progression-free survival was worse in one study (2.8% of studies testing progression-free survival). CONCLUSIONS AND RELEVANCE: Despite promising pre-clinical and population-based data, cardiovascular drugs and anti-inflammatory medications have overall not demonstrated benefit in the treatment or preventing recurrence of cancer. These findings may help guide future potential clinical trials involving these medications when applied in oncology.

Characterization of Thyroid Cancer among Hispanics in California, USA, from 2010 to 2020.

BACKGROUND: Previous studies on Hispanic thyroid cancer cases show sex disparities and an increased prevalence of large tumor sizes and nodal involvement. Here, we characterized Hispanic thyroid cancer cases in California. METHODS: We identified thyroid cancer cases from 2010 to 2020 using the California Cancer Registry by sex, race/ethnicity, histology, TNM stage, tumor size, lymph node involvement, and Charlson comorbidity score. The age-adjusted incidence rate (AAIR) and age-adjusted mortality rate (AAMR) for all causes of death were calculated. A Cox proportional hazards regression analysis was performed to evaluate the mortality risk from all causes of death by race. RESULTS: Overall, 56,838 thyroid cancer cases were identified, including 29.75% in Hispanics. Hispanics had the highest female-to-male incidence rate ratio (IRR 3.54) and the highest prevalence of T3/T4 tumor size (28.71%), the highest N1 nodal status (32.69%), and the highest AAMR (0.79 per 100,000 people). After adjusting for demographic and tumor covariates, compared to non-Hispanic White people, Hispanic ethnicity, with an HR of 1.22 (95% CI 1.18-1.25, p < 0.0001), remained a significant independent contributor to mortality risk. CONCLUSIONS: Hispanics had the greatest female-to-male IRR ratio, a greater prevalence of advanced disease features at diagnosis, along with the highest AAMR and increased mortality risk despite adjustments for demographic and tumor covariates. Further investigation into other risk factors is needed.

The Overall Survival Benefit in EV-302: Is Enfortumab Vedotin plus Pembrolizumab the New Frontline Standard of Care for Metastatic Urothelial Carcinoma?

Recent findings reported for the phase 3 EV-302 trial indicate a survival benefit from enfortumab vedotin plus pembrolizumab versus chemotherapy in metastatic urothelial carcinoma. We discuss several key points regarding post-protocol therapies, extending the duration of therapy, toxicity, and costs, all of which may have a bearing on how physicians and patients balance the benefit against the potential harms associated with this regimen.

A narrative review of antibody-drug conjugates in EGFR-mutated non-small cell lung cancer.

In the past 15 years, non-small cell lung cancer (NSCLC) treatment has changed with the discovery of mutations and the development of new targeted therapies and immune checkpoint inhibitors. Epidermal growth factor receptor (EGFR) was the first mutation in NSCLC to have a drug that was FDA-approved in 2013. Osimertinib, a third-generation tyrosine kinase inhibitor, is approved as first-line therapy for advanced NSCLC and in the adjuvant setting for Stage IB-IIIA resected NSCLC. However, resistance to osimertinib is inevitably an issue, and thus patterns of resistance to EGFR-mutated NSCLC have been studied, including MET amplification, EGFR C797X-acquired mutation, human epidermal growth factor 2 (HER2) amplification, and transformation to small cell and squamous cell lung cancer. Current management for EGFR-mutated NSCLC upon progression of EGFR TKI is limited at this time to chemotherapy and radiation therapy, sometimes in combination with the continuation of osimertinib. Antibody-drug conjugates (ADCs) are made up of a monoclonal antibody linked to a cytotoxic drug and are an increasingly popular class of drug being studied in NSCLC. Trastuzumab deruxtecan has received accelerated FDA approval in HER2-mutated NSCLC. ADCs offer a possible solution to finding a new treatment that could bypass the intracellular resistance mechanism. In this review article, we summarize the mechanism of ADCs and investigational ADCs for EGFR-mutated NSCLC, which include targets to MET amplification, HER3, Trop2, and EGFR, along with other ADC targets being investigated in NSCLC, and discuss future directions that may arise with ADCs in EGFR-mutated NSCLC.

A comparative study of spinal cord compression management in metastatic prostate cancer: Teaching versus non-teaching hospitals in the United States.

BACKGROUND: Spinal cord compression (SCC) in metastatic prostate cancer (MPC) is a critical complication and multiple factors influence the optimal therapeutic strategy. We investigated the differences in practice patterns between teaching hospitals (TH) and non-teaching hospitals (NTH) across the United States. METHOD: Using the National Inpatient Sample Database (NIS), we performed a retrospective study on hospitalizations with MPC and SCC between 2016 and 2020 in US. We compared demographic factors, comorbidities, treatment modalities, duration of hospitalization, financial expenditures, and mortality between TH and NTH. We also examined the patients' characteristics and outcomes in TH and NTH based on their chosen therapeutic strategy. RESULTS: We identified 11,380 admissions with metastatic prostate cancer and SCC; 9610 in TH and 1770 in NTH. The median cost of hospitalization was $21,922 in TH and $15,141 in NTH. Although the median age and Charlson comorbidity score did not differ between two groups, patients in TH were more likely to receive intervention (radiation or surgery) compared to NTH (Surgery: 28.2% in TH vs. 23.0% in NTH & Radiation: 12.1% in TH vs. 8.2% in NTH). Mortality was lower in TH than NTH (4.5% vs. 7.9%). In both TH and NTH, a higher proportion of patients with private insurance underwent surgery (TH: Surgery 25.1% vs. Radiation 18.8% & NTH: Surgery 27.0% vs. 6.9%). Black patients were more likely to receive radiation than surgery in TH (34.2% vs. 26.8%). CONCLUSION: This study showed a greater percentage of patients underwent surgical intervention at TH compared to NTH. Additionally, the type of insurance and racial background were associated with distinctive treatment approaches.

Starting and stopping cancer drugs: The need for randomized trials.

Precision oncology has gained widespread popularity over the past decade, and increasingly oncologists strive to provide the right treatment to the right patient. To date, precision efforts have focused on the specific mutational target(s), food/ drug interactions, functional oncology, or dose of drug given. Moreover, the tumor and blood samples of hundreds of thousands of patients with cancer have been sequenced in the United States alone with the goal of identifying and prescribing the most precise treatment. Despite this broad consideration of precision oncology, one neglected aspect of precision oncology is identifying the optimal start time and stopping point for cancer therapies. Is it possible to improve overall survival (OS) or quality of life for patients with more precise initiation and discontinuation of therapy? In this commentary, we review the historical basis to initiate, discontinue or switch therapies. We emphasize that largely these time points were selected arbitrarily, and subsequently constrained by historical accident. We highlight randomized efforts to better elucidate the time points in starting or stopping therapy. Finally, we provide suggestions for a research agenda on precision timing of anti-cancer drugs.

Hormonal treatment for newly diagnosed metastatic prostate cancer: a population-based study from the California cancer registry.

INTRODUCTION: To evaluate how often men with metastatic prostate cancer (mPC) receive standard of care treatment with androgen deprivation therapy (ADT). METHODS: Men aged ≥20 years with newly diagnosed mPC (stage IV) between 2010 and 2018 were identified using California Cancer Registry data. Receipt of hormonal therapy as initial cancer treatment was examined by patient/tumor characteristics at time of diagnosis. Chi-square tests and logistic regression, adjusted for covariates, were performed to assess association between receipt of hormonal therapy and patient/tumor characteristics. RESULTS: We identified 13,680 men with newly diagnosed mPC, of which 3637 had local metastasis (N1) only while 9596 had distant metastasis (M1) with or without N1 disease. 21.8 % (n = 2980) of men did not receive ADT. The highest rate of receiving ADT was among men between ages 75-84 (81.6%) and the lowest rate was in men over 85 (76.0%). Asian men had the largest proportion receiving ADT (n = 962, 81.5%) with remaining subgroups having similar proportion of men receiving ADT (76.8% to 77.2%). Once adjusted for covariates, regression results showed men with a higher Gleason score (8-10) were more likely to receive ADT (OR 2.04, 1.82-2.27, p = < 0.001) as well as men with distant sites of metastatic disease (OR 4.02, 3.62-4.46, p = < 0.001). Men residing in neighborhoods with the lowest socioeconomic status were least likely to receive ADT (OR 0.79, 0.68-0.93, p = 0.0032). No differences in receipt of ADT were observed by race/ethnicity. DISCUSSION: Despite significant advancements in the treatment of mPC in recent years, over one-fifth of patients did not receive ADT, which is the backbone for all new systemic therapies. This dataset might help address some of the prostate cancer care disparities in California.

Treatment approaches for FGFR-altered urothelial carcinoma: targeted therapies and immunotherapy.

The treatment of metastatic urothelial carcinoma has dramatically changed over the past decade with the approval of several therapies from multiple drug classes including immune checkpoint inhibitors, targeted therapies, and antibody drug conjugates. Although next generation sequencing of urothelial carcinoma has revealed multiple recurring mutations, only one targeted therapy has been developed and approved to date. Erdafitinib, a pan-fibroblast growth factor receptor (FGFR) inhibitor, has been approved for treating patients with select FGFR2 and FGFR3 alterations and fusions since 2019. Since then, emerging data has demonstrated efficacy of combining erdafitinib with immunotherapy in treating FGFR-altered urothelial carcinoma. Ongoing trials are evaluating the use of erdafitinib in non-muscle invasive urothelial carcinoma as well as in combination with enfortumab vedotin in the metastatic setting, while other FGFR targeted agents such as infigratinib, AZD4547, rogaratinib and pemigatinib continue to be in development. Future challenges will include strategies to overcome FGFR acquired resistance and efficacy and safety of combination therapies with erdafitinib and other FGFR targeted agents.

Treatment approaches for urachal cancer: Use of immunotherapy and targeted therapies.

Urachal cancer is a rare genitourinary malignancy that arises from the embryologic remnant of the urachus. The malignancy is considered to be aggressive, with no clear consensus on appropriate management for advanced disease. Although traditionally considered to be related to bladder cancer given its embryologic origin, several next generation sequencing studies have revealed the genomic profile of this genitourinary malignancy most closely resembles colorectal cancer. Moreover, these studies have identified potentially actionable mutations including EGFR, KRAS and MET. In addition, recent data suggests that immunotherapy may benefit some patients with advanced urachal cancer. Nonetheless, continued research is warranted to better understand how to treat this rare genitourinary cancer.