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Simple Summary: Novel hormonal therapies (such as abiraterone and enzalutamide) and docetaxel are approved treatments for metastatic prostate cancer. Upfront use of these agents has been shown to improve overall survival. However, we do not know the real-world treatment patterns of these agents or the comparative effectiveness of these agents after treatment with a prior novel hormonal therapy in patients with metastatic prostate cancer. In this large study, we found that most patients with metastatic prostate cancer received only androgen deprivation therapy as upfront therapy without novel hormonal therapies or docetaxel. In patients treated with one novel hormonal therapy, alternate novel hormonal therapy was the most common next therapy and was associated with improved overall survival over docetaxel with the caveat of this being a non-randomized comparison. The study's limitations also include its retrospective design. Background: Both novel hormonal therapies and docetaxel are approved for treatment of metastatic prostate cancer (mPC; in castration sensitive or refractory settings). Present knowledge gaps include lack of real-world data on treatment patterns in patients with newly diagnosed mPC, and comparative effectiveness of novel hormonal therapies (NHT) versus docetaxel after treatment with a prior NHT. Methods: Herein we extracted patient-level data from a large real-world database of patients with mPC in United States. Utilization of NHT or docetaxel for mPC and comparative effectiveness of an alternate NHT versus docetaxel after one prior NHT was evaluated. Comparative effectiveness was examined via Cox proportional hazards model with propensity score matching weights. Each patient's propensity for treatment was modeled via random forest based on 22 factors potentially driving treatment selection. Results: The majority of patients (54%) received only androgen deprivation therapy for mPC. In patients treated with an NHT, alternate NHT was the most common next therapy and was associated with improved median overall survival over docetaxel (abiraterone followed by docetaxel vs. enzalutamide (8.7 vs. 15.6 months; adjusted hazards ratio; aHR 1.32; p = 0.009; and enzalutamide followed by docetaxel vs. abiraterone (9.7 vs. 13.2 months aHR 1.40; p = 0.009). Limitations of the study include retrospective design. [ABSTRACT FROM AUTHOR]

Importance: Targeted therapies based on underlying tumor genomic susceptible alterations have been approved for patients with metastatic prostate cancer (mPC) and advanced urothelial carcinoma (aUC)., Objective: To assess trends and disparities in next-generation sequencing (NGS) testing among patients with mPC and aUC., Design, Setting, and Participants: This retrospective cohort study used an electronic health record-derived database to extract deidentified data of patients receiving care from US physician practices, hospital-affiliated clinics, and academic practices. Patients diagnosed with mPC or aUC between March 1, 2015, and December 31, 2022, were included., Exposures: Social determinants of health evaluated by race and ethnicity, socioeconomic status (SES), region, insurance type, and sex (for aUC)., Main Outcomes and Measures: The primary outcomes were (1) NGS testing rate by year of mPC and aUC diagnosis using Clopper-Pearson 2-sided 95% CIs and (2) time to NGS testing, which considered death as a competing risk. Cumulative incidence functions were estimated for time to NGS testing. Disparities in subdistributional incidence of NGS testing were assessed by race and ethnicity, SES, region, insurance type, and sex (for aUC) using the Fine-Gray modified Cox proportional hazards model, assuming different subdistribution baseline hazards by year of mPC and aUC diagnosis., Results: A total of 11 927 male patients with mPC (167 Asian [1.6%], 1236 Black [11.6%], 687 Hispanic or Latino [6.4%], 7037 White [66.0%], and 1535 other [14.4%] among 10 662 with known race and ethnicity) and 6490 patients with aUC (4765 male [73.4%]; 80 Asian [1.4%], 283 Black [4.8%], 257 Hispanic or Latino [4.4%], 4376 White [74.9%], and 845 other [14.5%] among 5841 with known race and ethnicity) were eligible and included. Both cohorts had a median age of 73 years (IQR, 66-80 years), and most underwent NGS testing before first-line treatment in the mPC cohort (1502 [43.0%]) and before second-line treatment in the aUC cohort (1067 [51.3%]). In the mPC cohort, the rates of NGS testing increased from 19.0% in 2015 to 27.1% in 2022, but Black patients (hazard ratio [HR], 0.75; 95% CI, 0.67-0.84) and Hispanic or Latino patients (HR, 0.70; 95% CI, 0.60-0.82) were less likely to undergo NGS testing. Patients with mPC who had low SES (quintile 1: HR, 0.74 [95% CI, 0.66-0.83]; quintile 2: HR, 0.89 [95% CI, 0.80-0.99]), had Medicaid (HR, 0.53; 95% CI, 0.38-0.74) or Medicare or other government insurance (HR, 0.89; 95% CI, 0.82-0.98), or lived in the West (HR, 0.81; 95% CI, 0.70-0.94) also were less likely to undergo testing. In the aUC cohort, the NGS rate increased from 14.1% in 2015 to 46.6% in 2022, but Black patients (HR, 0.76; 95% CI, 0.61-0.96) and those with low SES (quintile 1: HR 0.77 [95% CI, 0.66-0.89]; quintile 2: HR, 0.87 [95% CI, 0.76-1.00]) or Medicaid (HR, 0.72; 95% CI, 0.53-0.97) or Medicare or other government insurance (HR, 0.88; 95% CI, 0.78-0.99) were less likely to undergo NGS testing. Patients with aUC living in the South were more likely to undergo testing (HR, 1.29; 95% CI, 1.12-1.49)., Conclusions and Relevance: These findings suggest that although NGS tumor testing rates improved over time, the majority of patients still did not undergo testing. These data may help with understanding current disparities associated with NGS testing and improving access to standard-of-care health care services.

Importance: The treatment paradigm for advanced urothelial carcinoma (aUC) has undergone substantial transformation due to the introduction of effective, novel therapeutic agents. However, outcomes remain poor, and little is known about current treatment approaches and attrition rates for patients with aUC., Objectives: To delineate evolving treatment patterns and attrition rates in patients with aUC using a US-based patient-level sample., Design, Setting, and Participants: This retrospective cohort study used patient-level data from the nationwide deidentified electronic health record database Flatiron Health, originating from approximately 280 oncology clinics across the US. Patients included in the analysis received treatment for metastatic or local aUC at a participating site from January 1, 2011, to January 31, 2023. Patients receiving treatment for 2 or more different types of cancer or participating in clinical trials were excluded from the analysis., Main Outcomes and Measures: Frequencies and percentages were used to summarize the (1) treatment received in each line (cisplatin-based regimens, carboplatin-based regimens, programmed cell death 1 and/or programmed cell death ligand 1 [PD-1/PD-L1] inhibitors, single-agent nonplatinum chemotherapy, enfortumab vedotin, erdafitinib, sacituzumab govitecan, or others) and (2) attrition of patients with each line of therapy, defined as the percentage of patients not progressing to the next line., Results: Of the 12 157 patients within the dataset, 7260 met the eligibility criteria and were included in the analysis (5364 [73.9%] men; median age at the start of first-line treatment, 73 [IQR, 66-80] years). All patients commenced first-line treatment; of these, only 2714 (37.4%) progressed to receive second-line treatment, and 857 (11.8%) advanced to third-line treatment. The primary regimens used as first-line treatment contained carboplatin (2241 [30.9%]), followed by PD-1/PD-L1 inhibitors (2174 [29.9%]). The PD-1/PD-L1 inhibitors emerged as the predominant choice in the second- and third-line (1412 of 2714 [52.0%] and 258 of 857 [30.1%], respectively) treatments. From 2019 onward, novel therapeutic agents were increasingly used in second- and third-line treatments, including enfortumab vedotin (219 of 2714 [8.1%] and 159 of 857 [18.6%], respectively), erdafitinib (39 of 2714 [1.4%] and 28 of 857 [3.3%], respectively), and sacituzumab govitecan (14 of 2714 [0.5%] and 34 of 857 [4.0%], respectively)., Conclusions and Relevance: The findings of this cohort study suggest that approximately two-thirds of patients with aUC did not receive second-line treatment. Most first-line treatments do not include cisplatin-based regimens and instead incorporate carboplatin- or PD-1/PD-L1 inhibitor-based therapies. These data warrant the provision of more effective and tolerable first-line treatments for patients with aUC.