ABSTRACT
The treatment landscape of urothelial cancers has evolved in the last decade with the approval of chemotherapy, immune checkpoint inhibitors, targeted therapies, and antibody drug conjugates. Although improvements in response and survival have been achieved with these strategies, in some scenarios their benefit is still questionable. Current efforts to identify prognostic and predictive biomarkers are crucial for better patient selection and treatment outcomes. In this paper we will review the most promising biomarkers under investigation, such as molecular classifiers, genomic alterations, programmed cell death ligand 1 expression, tumor mutational burden, circulating tumor DNA, urinary biomarkers among others, for muscle invasive bladder cancer and metastatic urothelial cancers. Deeper understanding of these biomarkers will aid clinical decision-making and help tailor treatment strategies.
ABSTRACT
Urothelial carcinoma is the second most frequent genitourinary malignancy. Despite the poor prognosis, new treatment options have emerged and have expanded the therapeutic landscape for the disease. Although major improvements have been achieved, many patients experience rapid disease progression and low responses in subsequent lines of therapy. Sacituzumab govitecan is an ADC that targets Trop-2, which is highly expressed in urothelial cancers. Promising results in early clinical trials have led to further drug development which confirmed encouraging efficacy. Sacituzumab govitecan has been given accelerated approval in 2021 for patients with locally advanced and metastatic urothelial cancer who previously received a platinum containing chemotherapy and either a programmed death receptor-1 or programmed death ligand inhibitor. The results are promising, with encouraging efficacy and safety, however responses are not universal. There is a growing comprehension of mechanisms of resistance and predictive biomarkers that are crucial to improving outcomes. In this review, we summarize the current knowledge on antibody-drug conjugates and the clinical findings that led to the approval of Sacituzumab govitecan and discuss the therapeutic potential of new combinations, mechanisms of resistance and predictive biomarkers.
ABSTRACT
Background: With the ongoing expansion of life-prolonging therapies approved to treat advanced prostate cancer, there is currently an unmet need to better understand real-world treatment patterns and identify optimal treatment sequencing for men with metastatic castration-resistant prostate cancer (mCRPC). Methods: In this retrospective, observational cohort analysis, patients with confirmed mCRPC were identified in the Auditron claims database and used to describe mCRPC treatment patterns and trends in the Brazilian private healthcare system from 2014 to 2019. Demographics and clinical characteristics, prostate cancer stage at diagnosis, and type and number of treatment lines were evaluated. The primary endpoint was identification of the drugs used in first-line therapies in mCRPC, and the secondary endpoint included a description of sequential lines of therapy (second and third lines) in mCRPC. Results: A total of 168 electronic patient records were reviewed. Docetaxel was the most frequently used first-line treatment (35.7%), followed by abiraterone (33.3%) and enzalutamide (13.1%). Docetaxel, abiraterone, and enzalutamide also accounted for 34.6%, 28.0%, and 15.0%, respectively, of second-line therapies. In third-line therapies, cabazitaxel (26.1%), enzalutamide (23.9%), docetaxel (15.2%), and abiraterone (15.2%) were most commonly prescribed. Irrespective of stage at diagnosis, treatment patterns were similar once the disease progressed to the metastatic castration-resistance stage. Conclusions: Docetaxel was the most frequently utilized therapy for mCRPC treatment, followed by abiraterone and enzalutamide. Although the current analyses provide real-world insights into treatment patterns for patients with mCRPC in Brazil, additional real-world data are needed to further validate and expand on these findings.
