Clinical Efficacy of Enzalutamide vs Bicalutamide Combined With Androgen Deprivation Therapy in Men With Metastatic Hormone-Sensitive Prostate Cancer: A Randomized Clinical Trial.

Importance: Black patients have been underrepresented in prospective clinical trials of advanced prostate cancer. This study evaluated the efficacy of enzalutamide compared with bicalutamide, with planned subset analysis of Black patients with metastatic hormone-sensitive prostate cancer (mHSPC), which is a disease state responsive to androgen deprivation therapy (ADT). Objective: To compare the efficacy of enzalutamide vs bicalutamide in combination with ADT in men with mHSPC, with a subset analysis of Black patients. Design, Setting, and Participants: In this randomized clinical trial, a phase 2 screening design enabled a nondefinitive comparison of the primary outcome by treatment. Patients were stratified by race (Black or other) and bone pain (present or absent). Accrual of at least 30% Black patients was required. This multicenter trial was conducted at 4 centers in the US. Men with mHSPC with no history of seizures and adequate marrow, renal, and liver function were eligible. Data analysis was performed from February 2019 to March 2020. Interventions: Participants were randomized 1:1 to receive oral enzalutamide (160 mg daily) or bicalutamide (50 mg daily) in addition to ADT. Main Outcomes and Measures: The primary end point was the 7-month prostate-specific antigen (PSA) response (SMPR) rate, a previously accepted surrogate for overall survival (OS) outcome. Secondary end points included adverse reactions, time to PSA progression, and OS. Results: A total of 71 men (median [range] age, 65 [51-86] years) were enrolled; 29 (41%) were Black, 41 (58%) were White, and 1 (1%) was Asian. Thirty-six patients were randomized to receive enzalutamide, and 35 were randomized to receive bicalutamide. Twenty-six patients (37%) had bone pain and 37 patients (52%) had extensive disease. SMPR was achieved in 30 of 32 patients (94%; 95% CI, 80%-98%) taking enzalutamide and 17 of 26 patients (65%; 95% CI, 46%-81%) taking bicalutamide (P = .008) (difference, 29%; 95% CI, 5%-50%). Among Black patients, the SMPR was 93% (95% CI, 69%-99%) among those taking enzalutamide and 42% (95% CI, 19%-68%) among those taking bicalutamide (P = .009); among non-Black patients, the SMPR was 94% (95% CI, 74%-99%) among those taking enzalutamide and 86% (95% CI, 60%-96%) among those taking bicalutamide. The 12-month PSA response rates were 84% with enzalutamide and 34% with bicalutamide. Conclusions and Relevance: The findings of this randomized clinical trial comparing enzalutamide with bicalutamide suggest that enzalutamide is associated with improved outcomes compared with bicalutamide, in terms of the rate and duration of PSA response, in Black patients with mHSPC. Trial Registration: ClinicalTrials.gov Identifier: NCT02058706.

Hypercalcemia Is of Uncertain Significance in Patients With Advanced Adenocarcinoma of the Prostate.

Hypercalcemia in the setting of prostate cancer is rare with an uncertain pathophysiology and more research is needed into the role of parathyroid hormone-related peptide as a growth factor and possibly target-directed monoclonal antibody therapies.

Effect of Exposure to Agent Orange on the Risk of Monoclonal Gammopathy and Subsequent Transformation to Multiple Myeloma: A Single-Center Experience From the Veterans Affairs Hospital, Detroit.

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is an indolent, premalignant plasma cell disorder with the potential of transforming into symptomatic multiple myeloma (MM). There are multiple risk factors that contribute to transformation. Agent Orange (AO) has been linked with multiple malignant and nonmalignant conditions. PATIENTS AND METHODS: We conducted a retrospective chart review of patients with monoclonal gammopathy who were seen at John D. Dingell Veterans Affairs Medical Center (Detroit, Michigan) between 2005 and 2015 with MGUS, smoldering multiple myeloma, and MM. We explored baseline patient characteristics and explored AO exposure. Dates of diagnosis, dates of progression, and expiration dates were recorded to time to progression and overall survival (OS). RESULTS: We identified 211 patients with monoclonal gammopathy; 96% were male and 122 were African American. Eleven patients had reported AO exposure. Cumulative risk of progression in the overall population was 1.4% at 1 year. Risk of transformation in the population exposed to AO was significantly higher with a hazard ratio (HR) of 11.19 (95% confidence interval [CI], 2.10-59.47; P = .005). OS was numerically shorter in AO-exposed patients with a median OS of 7 years compared with 11.1 years in those not exposed. However, AO exposure was not associated with OS in multivariable analysis (HR, 0.50; 95% CI, 0.07-3.83; P = .508). CONCLUSION: Monoclonal gammopathy is a premalignant condition with the risk of progressing to MM. Exposure to AO has been implicated in multiple conditions including MM. Our study demonstrates an increased risk of progression in exposed patients.

Participation and survival of geriatric patients in Phase I clinical trials: the Karmanos Cancer Institute (KCI) experience.

BACKGROUND: Geriatric cancer patients (age 65 or older) comprise a majority of cancer cases in the United States, yet they are underrepresented in therapeutic clinical trials. It is therefore important to increase our understanding of their participation, survival outcomes, and recruitment barriers. This study aims to describe the demographics, treatment, toxicity, and overall survival (OS) of all patients ≥ 65 years of age who presented to the Phase I Clinical Trials service at Karmanos Cancer Institute (KCI). METHODS: A retrospective chart review was performed of all referred and seen patients ≥ 65 years of age at Phase I clinical service at KCI between 1995-2005. Data on demographics, co-morbidities, tumor type, reason not enrolled, toxicities and OS were obtained. RESULTS: A total of 216 patients met the study criteria. The median age was 71 years. 114 (59%) patients were performance status 1. 102 (47%) patients were enrolled and of those 95 (44%) patients were treated. More than half of the patients failed to enroll with predominant reasons being protocol ineligibility (30%), loss to follow up (12%), patient refusal (8%), or unavailability of trial (2%). The median OS duration of treated patients was 8.4 months (95% CI: 6.2-10.5). This was significantly longer than the patients who failed to enroll or did not receive treatment (p < 0.0001). CONCLUSION: This study suggests that elderly patients who were treated on a Phase I clinical trial(s) at our institution survived significantly longer than our elderly patients who did not receive treatment.

Impact of race, age, and socioeconomic status on participation in pancreatic cancer clinical trials.

OBJECTIVES: Over 18 years, 7 phase 2 trials in advanced pancreatic cancer (APC) were conducted at Karmanos Cancer Institute (KCI). We sought factors that influenced the selection of patients for clinical trials and explored differences in overall survival (OS) of patients treated on clinical trials versus standard of care. METHODS: The target population was patients with APC diagnosed between January 1, 1986, and December 31, 2003. Patients were divided into 3 mutually exclusive groups: treated on clinical trials at KCI (t-KCI), treated at KCI but not on a clinical trial (KCI), or treated at non-KCI institutions (n-KCI). RESULTS: Eight thousand two hundred thirty patients met study criteria: 6470 n-KCI, 1642 KCI, and 118 t-KCI. Significant differences were observed across the 3 groups with respect to age, race, stage, grade, and socioeconomic status. Median OS was higher in t-KCI (8.5 months) than in KCI (5.0 months) or n-KCI (2.8 months) and could not be accounted for by variations in baseline characteristics. CONCLUSIONS: Patients enrolled on clinical trials were younger, had better socioeconomic status, and were less often African American. Patients with APC treated at academic institutions may have longer OS than patients treated in the community. Clinical trials seem to offer a survival advantage for patients with APC.