Abstract
Background
In the ARASENS trial (NCT02799602), darolutamide in combination with androgen-deprivation therapy (ADT) and docetaxel significantly reduced the risk of death by 32.5% (HR, 0.68; 95% CI, 0.57-0.80; P < .0001) compared with placebo plus ADT with docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC). We present efficacy and safety of darolutamide versus placebo in Black patients from ARASENS.
Patients and Methods
Patients with mHSPC were randomized 1:1 to darolutamide 600 mg or placebo twice daily in combination with ADT and docetaxel. The primary endpoint was overall survival. Key secondary endpoints included time to castration-resistant prostate cancer (CRPC) and safety.
Results
In ARASENS, 54 Black patients received darolutamide (n = 26) or placebo (n = 28) plus ADT and docetaxel. In Black patients, overall survival favored darolutamide versus placebo (median, not reached vs. 38.7 months; stratified HR, 0.41; 95% CI, 0.17-1.02), with 4-year survival rates of 62% versus 41%. The darolutamide group also had longer time to CRPC compared with the placebo group (median, not reached vs .12.6 months; HR, 0.09; 95% CI, 0.02-0.30). The safety profile of darolutamide in Black patients was consistent with that observed for the overall ARASENS population (grade 3/4 treatment-emergent adverse events, TEAEs: 61.5% vs. 66.1%; serious TEAEs: 42.3% vs. 44.8%).
Conclusion
In this small population of Black patients with mHSPC from the ARASENS trial, darolutamide was associated with an improvement in survival and time to CRPC and was well tolerated. Efficacy and safety findings in Black patients were consistent with the overall ARASENS population.
Keywords: androgen receptor inhibitor, darolutamide, metastatic hormone-sensitive prostate cancer, Black, survival analyses, safety
In the ARASENS trial, darolutamide in combination with androgen-deprivation therapy (ADT) and docetaxel significantly reduced the risk of death compared with placebo plus ADT with docetaxel in patients with metastatic hormone-sensitive prostate cancer. This article presents efficacy and safety results for darolutamide versus placebo in Black patients from ARASENS.
Implications for Practice.
Prostate cancer that has spread to other parts of the body and can be treated with hormonal therapy, including androgen-deprivation therapy (ADT), is called metastatic hormone-sensitive prostate cancer (mHSPC). Based on results of the phase III ARASENS study, darolutamide is an approved treatment for mHSPC when used in combination with ADT and docetaxel (chemotherapy). This report provides information on the effect of darolutamide, ADT, and docetaxel in the 54 Black patients in ARASENS. In these patients, darolutamide was well tolerated and lowered the risks of patients dying and their cancer progressing. These results are consistent with the overall ARASENS population.
Introduction
Globally, prostate cancer is the second most common malignancy behind lung cancer in men and ranks first in incidence among men in the United States.1,2 Black people are disproportionately affected by prostate cancer, with higher incidence and mortality rates versus other racial/ethnic groups. These higher rates have been attributed to multiple factors including longstanding inequalities in wealth leading to differences in risk factor exposure, access to healthcare, and equitable cancer prevention, screening, and treatment.2 White participants are disproportionately represented in genomic databases, resulting in higher rates of genomically aggressive cancer observed among Black men with prostate cancer.2,3 Data from the Surveillance, Epidemiology, and End Results (SEER) database and the Veterans Affairs healthcare system, primarily in patients with non-metastatic disease, suggest that when disparities in access to care and known prognostic factors are controlled, outcomes are similar between Black patients and their White counterparts.4-6 However, data on outcomes in Black patients with metastatic prostate cancer are scarce.7
Metastatic prostate cancer has a 5-year survival rate of approximately 30% compared with >99% for localized and regional disease,2 highlighting a need for treatments to prolong survival, and delay disease progression in patients with metastatic disease. For patients with metastatic hormone-sensitive prostate cancer (mHSPC), clinical outcomes have improved with the combination of androgen-deprivation therapy (ADT) plus an androgen receptor pathway inhibitor and/or docetaxel.8-13 However, limited data are available for Black participants from these clinical trials.7 Results of the CHAARTED trial comparing ADT alone or in combination with docetaxel in patients with mHSPC showed shorter median survival among Black patients (n = 76) versus White non-Hispanic patients (n = 595) receiving ADT alone (34.1 vs. 45.2 months) and similar survival between these racial groups receiving combination therapy (57.6 vs. 58.1 months).14 Pooled analyses of phase III trials evaluating docetaxel and prednisone regimens for metastatic castration-resistant prostate cancer (mCRPC) indicated approximately 6% of patients were Black and showed similar outcomes in this group compared with White patients.7,15
Darolutamide, a structurally distinct and highly potent androgen receptor inhibitor, has demonstrated low blood-brain barrier penetration and a limited potential for clinically relevant drug-drug interactions.16,17 In the phase III ARASENS trial in patients with mHSPC, darolutamide in combination with ADT and docetaxel significantly reduced the risk of death by 32.5% (hazard ratio, HR, 0.68; 95% CI, 0.57-0.80; P < .0001) and significantly delayed onset of castration-resistant prostate cancer (CRPC) (HR, 0.36; 95% CI, 0.30-0.42; P < .001) versus ADT and docetaxel alone.13 Incidences of treatment-emergent adverse events (TEAEs) were similar in the 2 treatment groups and incidences of the most common TEAEs were highest during the overlapping docetaxel treatment period and progressively decreased thereafter. We present efficacy and safety results for the subgroup of Black patients from ARASENS.
Patients and Methods
Trial Design and Patients
ARASENS was a randomized, double-blind, placebo-controlled, phase III trial of darolutamide versus placebo in combination with ADT and docetaxel in patients with mHSPC. Patients were randomized into the trial between 2016 and 2018 at 286 centers in 23 countries worldwide, and trial data readout occurred in 2021. Details of the trial design and methodology and CONSORT flow diagram of patient disposition have been published (Supplementary Fig. S1).13
The trial protocol was approved by the institutional review board at each participating center. The trial was conducted in accordance with the principles of the Declaration of Helsinki and the International Council for Harmonisation Good Clinical Practice guidelines. Written informed consent was provided by all patients.
Adult patients were required to have mHSPC with metastases beyond regional lymph nodes only detected on bone scanning, contrast-enhanced computed tomography, or magnetic resonance imaging. Patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and were considered candidates for treatment with ADT and docetaxel in the opinion of the investigator. Patients were excluded if they had received prior therapy with ADT more than 12 weeks before randomization, radiotherapy within 2 weeks of randomization, or second-generation androgen receptor pathway inhibitors, chemotherapy, or immunotherapy for prostate cancer before randomization.
All patients received standard ADT (or underwent orchiectomy) within 12 weeks of randomization and docetaxel within 6 weeks after randomization as previously described.13 Patients were equally randomized to darolutamide 600 mg twice daily or placebo, with stratification based on extent of metastasis (M1a: nonregional lymph nodes only, M1b: bone metastases with or without lymph node metastases, or M1c: visceral metastases with or without lymph node or bone metastases) and alkaline phosphatase level based on the upper level of normal (<ULN vs. ≥ULN). Prespecified subgroup analyses included patients with de novo and recurrent disease. Treatment was continued until symptomatic disease progression, a change in chemotherapy, unacceptable toxicity, decision by patient or physician, death, or nonadherence.
Endpoints
Patients were assessed every 12 weeks for evidence of disease progression and treatment-emergent adverse events (TEAEs). Overall survival was the primary endpoint and time to CRPC was the first of several secondary endpoints analyzed hierarchically. Safety was assessed as TEAEs that occurred during treatment, including those commonly associated with androgen receptor pathway inhibitors (fatigue, vasodilation/flushing, hypertension, diabetes/hyperglycemia, cardiac disorders, fall, depressed mood disorders, rash, fracture, decreased weight, mental impairment, and breast disorders/gynecomastia).
Statistical Analyses
Patient demographics, baseline characteristics, and TEAEs are reported descriptively for the subgroup of Black patients. The exposure-adjusted incidence rate (EAIR) of TEAEs is defined as the number of patients with a given TEAE divided by the treatment duration (in years) of all patients in the respective subgroup, expressed in 100 patient-years (PY).
Overall survival and time to CPRC for this subgroup were analyzed post hoc using Kaplan-Meier estimates to compute medians and 95% CIs. A Cox regression model, stratified by extent of disease and alkaline phosphatase (<ULN vs. ≥ULN), was used to calculate HRs and 95% CIs for comparison between treatment arms.
Results
Patients
Of 1305 patients in the overall ARASENS trial population, 54 were Black, of which 26 received darolutamide and 28 received placebo. Black patients represented 14.8% (36/244) of those enrolled in North America, 0.2% (1/473) from the Asia-Pacific region, and 2.9% (17/588) from the rest of the world. Demographics and baseline clinical characteristics of the Black subgroup were generally similar compared with the overall population, except that a greater proportion of Black patients were younger than 65 years of age (57.4% vs. 36.6%), had an ECOG performance status of 1 (37.0% vs. 28.7%), and had recurrent disease (24.1% vs. 12.9%; Table 1). Median prostate-specific antigen levels at baseline were similar in Black patients compared with all patients (35.9 vs. 27.6 μg/L), but alkaline phosphatase levels were lower in Black patients (109.5 vs. 143.0 U/L).
Table 1.
Patient demographics and clinical characteristics at baseline.
| Characteristic at baseline | Black subgroup | Overall populationa | ||
|---|---|---|---|---|
| Darolutamide + ADT + docetaxel (n = 26) |
Placebo + ADT + docetaxel (n = 28) |
Darolutamide + ADT + docetaxel (n = 651) |
Placebo + ADT + docetaxe (n = 654a) |
|
| Age, median (range), yr | 63.5 (52-84) | 63 (47-82) | 67 (41-89) | 67 (42-86) |
| Age group, n (%) | ||||
| <65 yr | 15 (57.7) | 16 (57.1) | 243 (37.3) | 234 (35.8) |
| 65-74 yr | 9 (34.6) | 11 (39.3) | 303 (46.5) | 306 (46.8) |
| ≥75 yr | 2 (7.7) | 1 (3.6) | 105 (16.1) | 114 (17.4) |
| ECOG performance status, n (%) | ||||
| 0 | 15 (57.7) | 19 (67.9) | 466 (71.6) | 462 (70.6) |
| 1 | 11 (42.3) | 9 (32.1) | 185 (28.4) | 190 (29.1) |
| Gleason score at initial diagnosis, n (%) | ||||
| <8 | 6 (23.1) | 5 (17.9) | 122 (18.7) | 118 (18.0) |
| ≥8 | 19 (73.1) | 21 (75.0) | 505 (77.6) | 516 (78.9) |
| Missing | 1 (3.8) | 2 (7.1) | 24 (3.7) | 20 (3.1) |
| Metastatic stage at initial diagnosis, n (%) | ||||
| De novo | 20 (76.9) | 20 (71.4) | 558 (85.7) | 566 (86.5) |
| Recurrent | 5 (19.2) | 8 (28.6) | 86 (13.2) | 82 (12.5) |
| Distant metastasis not assessed | 1 (3.8) | 0 | 7 (1.1) | 6 (0.9) |
| Metastasis stage at screening, n (%) | ||||
| M1a, nonregional LN only | 1 (3.8) | 1 (3.6) | 23 (3.5) | 16 (2.4) |
| M1b, bone ± LN | 20 (76.9) | 23 (82.1) | 517 (79.4) | 520 (79.5) |
| M1c, visceral ± LN or bone | 5 (19.2) | 4 (14.3) | 111 (17.1) | 118 (18.0) |
| PSA, median (range), ng/mLb | 38.2 (0.0-949.0) | 33.0 (0.2-5255.0) | 30.3 (0.0-9219.0) | 24.2 (0.0-11 947.0) |
| ALP, median (range), U/Lb | 113.5 (59-1031) | 107.0 (55-2065) | 148 (40-4885) | 140 (36-7680) |
| ALP, n (%)b | ||||
| <ULN | 14 (53.8) | 17 (60.7) | 209 (44.5) | 291 (44.5) |
| ≥ULN | 12 (46.2) | 11 (39.3) | 361 (55.5) | 363 (55.5) |
Data for the overall population are from the New England Journal of Medicine, Smith MR, Hussain M, Saad F, et al, Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer, volume 386, pages 1132-1142. Copyright © 2022 Massachusetts Medical Society. Reprinted with permission.
aOne patient randomized to placebo but who received darolutamide was included in the placebo group for the full analysis set.
bCentrally assessed; samples were collected while patients were receiving ADT.
Abbreviations: ADT: androgen-deprivation therapy; ALP: alkaline phosphatase; ECOG: Eastern Cooperative Oncology Group; LN: lymph node; PSA: prostate-specific antigen; ULN: upper limit of normal.
Median treatment duration was longer for darolutamide versus placebo among Black patients (29.6 vs. 12.4 months) and in the overall population (41.0 vs. 16.7 months), although treatment durations were longer in the overall population.13 Six cycles of docetaxel treatment were completed by similar proportions of patients in the darolutamide (77%) and placebo (75%) groups, which were slightly lower than rates observed in the overall population (87.6% and 85.5%, respectively).13
Efficacy
In Black patients, overall survival favored darolutamide in combination with ADT and docetaxel versus ADT and docetaxel alone, with a stratified hazard ratio of 0.41 (95% CI, 0.17-1.02; Fig. 1A). Median survival was not reached in the darolutamide group and was 38.7 months in the placebo group. Four-year survival rates were 62% for Black patients receiving darolutamide versus 41% for those receiving placebo. Survival results in the subgroup were consistent with those in the overall ARASENS population (Fig. 1B).
Figure 1.
Overall survival in the (A) Black subgroup and (B) overall population. Analysis was conducted after 533 deaths (darolutamide, 229; placebo, 304) occurred in the overall population. Abbreviations: ADT: androgen-deprivation therapy; CI: confidence interval; NE: not estimable.
Time to CRPC was increased for Black patients receiving darolutamide compared with those receiving placebo (HR, 0.09; 95% CI, 0.02-0.30; Fig. 2A). The median time to CRPC was not reached in the darolutamide group and was 12.6 months in the placebo group. Results were consistent with the overall population (Fig. 2B).
Figure 2.
Time to castration-resistant prostate cancer in the (A) Black subgroup and (B) overall population. Abbreviations: ADT: androgen-deprivation therapy; CI: confidence interval; NE: not estimable.
Safety
The safety profile of darolutamide in Black patients was consistent with that observed for all patients (Table 2). In this small subgroup of 54 patients, despite longer treatment duration with darolutamide versus placebo, numbers of patients with grade 3 or 4 adverse events (16 vs. 17), serious adverse events (11 vs. 7), and discontinuations of darolutamide or placebo due to adverse events (5 vs. 4) were similar between treatment groups.
Table 2.
Incidence of treatment-emergent adverse events.
| TEAE, n (%) | Black subgroup | Overall populationa | ||
|---|---|---|---|---|
| Darolutamide + ADT + docetaxel (n = 26) |
Placebo + ADT + docetaxel (n = 28) |
Darolutamide + ADT + docetaxel (n = 652) |
Placebo + ADT + docetaxel (n = 650a) |
|
| Any | 26 (100.0) | 27 (96.4) | 649 (99.5) | 643 (98.9) |
| Worst grade | ||||
| Grade 1 or 2 | 8 (30.8) | 10 (35.7) | 190 (29.1) | 204 (31.4) |
| Grade 3 or 4 | 16 (61.5) | 17 (60.7) | 431 (66.1) | 413 (63.5) |
| Grade 5 | 2 (7.7) | 0 | 27 (4.1) | 26 (4.0) |
| Serious | 11 (42.3) | 7 (25.0) | 292 (44.8) | 275 (42.3) |
| Leading to discontinuation of: | ||||
| Darolutamide/placebo | 5 (19.2) | 4 (14.3) | 88 (13.5) | 69 (10.6) |
| Exposure-adjusted incidence rate, per 100 patient yearsb | 8.1 | 11.2 | 5.1 | 5.7 |
Data for the overall population are from the New England Journal of Medicine, Smith MR, Hussain M, Saad F, et al, Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer, volume 386, pages 1132-1142. Copyright © 2022 Massachusetts Medical Society. Reprinted with permission.
aThree randomized patients (all in the placebo group) were never treated and were excluded from the safety analysis set. One patient randomized to placebo but who received darolutamide was included in the darolutamide group for the safety analysis set.
bExposure-adjusted incidence rate is defined as the number of patients with a given TEAE divided by the total darolutamide/placebo treatment duration for all patients in years.
Abbreviations: ADT: androgen-deprivation therapy; TEAE: treatment-emergent adverse event.
Incidence rates of most TEAEs commonly associated with androgen receptor pathway inhibitors were similar between treatment groups and generally consistent with incidences observed in the overall population (Table 3). When they were adjusted for the longer duration of darolutamide treatment, the EAIRs between treatment groups for hypertension, cardiac disorders, bone fracture, and depressed mood disorders were similar or decreased.
Table 3.
Incidence of treatment-emergent adverse events associated with androgen receptor pathway inhibitors.
| TEAE, n (%) | Black subgroup | Overall populationa | ||||||
|---|---|---|---|---|---|---|---|---|
| Darolutamide + ADT + docetaxel (n = 26) |
Placebo + ADT + docetaxel (n = 28) |
Darolutamide + ADT + docetaxel (n = 652) |
Placebo + ADT + docetaxel (n = 650a) |
|||||
| n (%) | EAIR/100 PYb | n (%) | EAIR/100 PYb | n (%) | EAIR/100 PYb | n (%) | EAIR/100 PYb | |
| Fatigue | 13 (50.0) | 21.1 | 15 (53.6) | 42.1 | 216 (33.1) | 12.5 | 214 (32.9) | 17.8 |
| Vasodilation/flushing | 8 (30.8) | 13.0 | 15 (53.6) | 42.1 | 133 (20.4) | 7.7 | 141 (21.7) | 11.7 |
| Rash | 2 (7.7) | 3.2 | 2 (7.1) | 5.6 | 108 (16.6) | 6.2 | 88 (13.5) | 7.3 |
| Diabetes/hyperglycemia | 4 (15.4) | 6.5 | 7 (25.0) | 19.6 | 99 (15.2) | 5.7 | 93 (14.3) | 7.7 |
| Hypertension | 8 (30.8) | 13.0 | 6 (21.4) | 16.8 | 89 (13.7) | 5.1 | 60 (9.2) | 5.0 |
| Cardiac disorders | 4 (15.4) | 6.5 | 3 (10.7) | 8.4 | 71 (10.9) | 4.1 | 76 (11.7) | 6.3 |
| Bone fracture | 2 (7.7) | 3.2 | 1 (3.6) | 2.8 | 49 (7.5) | 2.8 | 33 (5.1) | 2.7 |
| Fall | 4 (15.4) | 6.5 | 0 | 0 | 43 (6.6) | 2.5 | 30 (4.6) | 2.5 |
| Mental impairment disorders | 1 (3.8) | 1.6 | 0 | 0 | 23 (3.5) | 1.3 | 15 (2.3) | 1.2 |
| Decreased weight | 1 (3.8) | 1.6 | 3 (10.7) | 8.4 | 22 (3.4) | 1.3 | 35 (5.4) | 2.9 |
| Depressed mood disorders | 3 (11.5) | 4.9 | 2 (7.1) | 5.6 | 21 (3.2) | 1.2 | 24 (3.7) | 2.0 |
| Breast disorders/gynecomastia | 0 | 0 | 2 (7.1) | 5.6 | 21 (3.2) | 1.2 | 10 (1.5) | 0.8 |
Data for the overall population are from the New England Journal of Medicine, Smith MR, Hussain M, Saad F, et al, Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer, volume 386, pages 1132-1142. Copyright © 2022 Massachusetts Medical Society. Reprinted with permission.
aThree randomized patients (all in the placebo group) were never treated and were excluded from the safety analysis set. One patient randomized to placebo but who received darolutamide was included in the darolutamide group for the safety analysis set.
bExposure-adjusted incidence rate is defined as the number of patients with a given TEAE divided by the total darolutamide/placebo treatment duration for all patients in years.
Abbreviations: ADT: androgen-deprivation therapy; EAIR: exposure-adjusted incidence rate; PY: patient-years; TEAE: treatment-emergent adverse event.
Discussion
In ARASENS, darolutamide significantly improved overall survival and key secondary endpoints compared with placebo and was well tolerated with no added toxicity when combined with ADT and docetaxel in patients with mHSPC.13,18 The results of this subgroup analysis of Black patients in ARASENS are consistent with results from the overall population showing a survival benefit with darolutamide. Four-year survival rates were 62% and 63% with darolutamide in the subgroup and overall populations, respectively, compared with 41% and 50% with placebo. Darolutamide also increased the time to castration-resistance versus placebo in Black patients. The favorable safety and tolerability profile of darolutamide was confirmed in Black patients with mHSPC. Most patients were able to receive 6 cycles of docetaxel therapy in both treatment groups. Incidence rates of grade 3 or 4 and serious TEAEs were similar across treatment groups, despite longer treatment with darolutamide versus placebo, and consistent with the overall population. No new safety findings were observed.
Clinical trials combining standard ADT with docetaxel and/or novel androgen receptor pathway inhibitors have enrolled small numbers of Black patients with mHSPC, providing limited efficacy and safety information for this population. The CHAARTED trial of ADT with or without docetaxel included 9.6% of patients who were Black,8 while TITAN and ARCHES trials of apalutamide and enzalutamide included 1.8% and 1.4%, respectively.19,20 Overall survival in CHAARTED was similar for Black patients and White patients who received ADT and docetaxel (57.6 vs. 58.1 months) but slightly lower for Black versus White patients who received ADT alone (34.1 v.s 45.2 months).14 Results for TITAN and ARCHES by race subgroup have not been published. A real-world analysis of health record data identified 168 patients with mHSPC who received treatment with upfront docetaxel or abiraterone before any other systemic therapy, of which 92 (54.8%) patients were Black and 76 (45.2%) were non-Black, including 69 White patients and 7 Asian or Hispanic patients.21 Overall survival at 12 months among Black patients was 89.2% for docetaxel and 97.5% for abiraterone, with no significant difference versus the non-Black population (95.5% and 92.6%, respectively). A retrospective study across 7 academic institutions in the US reported favorable time to CRPC and overall survival for 107 Black patients with mHSPC who received ADT-based regimens, including first-generation anti-androgens, novel androgen receptor pathway inhibitors, and/or docetaxel.22 These findings from the literature suggest that Black patients can achieve similar benefits from treatments for mHSPC as observed for non-Black patients. Several larger studies provide further support in patients with metastatic prostate cancer not specifically defined as mHSPC. An analysis of the US National Cancer Database found similar survival outcomes for Black (n = 5932) and White (n = 24 659) patients with metastatic prostate cancer.23 A meta-analysis of phase III trials of patients with metastatic CRPC showed similar median survival times for Black patients compared with White patients (21 months) with the pooled hazard ratio showing a survival benefit in Black patients (HR 0.81; 95% CI, 0.72-0.91).7 Further analyses of these pooled data indicated no differences between racial groups in progression-free survival (PFS) distributions, median PFS, prostate-specific antigen decline from baseline of 50% or more, and overall response rates.15
This analysis of Black patients in ARASENS was conducted post hoc in a small population. Our findings add valuable information to the growing body of work evaluating the treatment of advanced prostate cancer in this population. Current information suggests that equal access to care leads to achievement of comparable outcomes for Black patients as achieved by White patients.4-6 However, racial disparities in prostate cancer incidence and mortality continue to exist and have been linked to social, economic, environmental, and genetic factors.24 Patient numbers for Black participants remain small in clinical trials, and we strongly encourage all clinical research investigators to optimize racial and ethnic accrual for both existing and future trials. Findings from a pooled analysis of 7 phase III trials in CRPC underscore the importance of diverse participation in clinical trials to ensure equitable access to novel therapies and to accurately assess treatment efficacy in diverse populations. Out of a total of 7275 patients enrolled in the 7 trials from this analysis, only 3.3% were Black.25 By mandating diversity in clinical trials, we can help address persistent racial disparities in prostate cancer outcomes and develop more tailored interventions that improve health outcomes for all individuals affected by this disease.
Conclusions
In Black patients with mHSPC, darolutamide in combination with ADT and docetaxel improved overall survival and time to CRPC compared with ADT and docetaxel alone and was well tolerated. Results in this subgroup of patients were consistent with those of the overall ARASENS population.
Supplementary Material
Supplementary material is available at The Oncologist online.
Acknowledgments
Data reported in this article were presented at the 15th American Association for Cancer Research Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and The Medically Underserved, September 16-19, 2022, in Philadelphia, PA, USA. The authors thank the patients and their families, and all of the investigators involved in the ARASENS trial. Writing and editorial support in the development of this manuscript was provided by Michelle McDermott, PharmD of OPEN Health Communications (London, UK), with financial support from Bayer HealthCare (Whippany, NJ, USA). Statistical analyses were provided by Kevin Clark, MPH, MS, PT, of Bayer and Lei Li, MSc, of CHRESTOS Concept GmbH & Co.KG. The authors retained full editorial control over the content of the manuscript and the decision to publish.
Contributor Information
Neal D Shore, Carolina Urologic Research Center/Genesis Care, Myrtle Beach, SC, USA.
Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
Fred Saad, Centre Hospitalier de l’Université de Montréal, University of Montreal, Montreal, Quebec, Canada.
Karim Fizazi, Institut Gustave Roussy, University of Paris-Saclay, Villejuif, France.
Cora N Sternberg, Englander Institute for Precision Medicine, Weill Cornell Department of Medicine, Meyer Cancer Center, New York-Presbyterian Hospital, New York, NY, USA.
David Crawford, University of California San Diego School of Medicine, San Diego, CA, USA.
Bertrand Tombal, Division of Urology, IREC, Cliniques Universitaires Saint Luc, UCLouvain, Brussels, Belgium.
Luke Nordquist, XCancer/GU Research Network, Omaha, NE, USA.
Michael Cookson, University of Oklahoma Stephenson Cancer Center, Oklahoma City, OK, USA.
Frank Verholen, Bayer Consumer Care, Basel, Switzerland.
Jay Jhaveri, Bayer Healthcare Pharmaceuticals, Inc., Whippany, NJ, USA.
Shankar Srinivasan, Bayer Healthcare Pharmaceuticals, Inc., Whippany, NJ, USA.
Matthew R Smith, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Funding
This study was funded by Bayer and Orion Pharma.
Conflict of Interest
Neal D. Shore: Consulting or advisory roles: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb/Sanofi, Boston Scientific, CG Oncology, Clarity Pharmaceuticals, Clovis Oncology, Dendreon, Exact Imaging, FerGene, Ferring, Foundation Medicine, Genesis Cancer Care, Genzyme, InVitae, Janssen, Lantheus Medical Imaging, Lilly, MDxHealth, Medivation/Astellas, Merck, Myovant, Myriad Genetics, Nymox, Pacific Edge Biotechnology, Pfizer, Phosphorus, Photocure, PeerView, Propella Therapeutics, Sanofi, Sema4, Sesen Bio, Specialty Networks, Telix, Tempus, Tolmar, Urogen Pharma, and Vaxiion; Speaker bureaus: Astellas, AstraZeneca, Bayer, Clovis Oncology, Dendreon, Foundation Medicine, Guardant Health, Janssen, Merck, and Pfizer; Expert testimony: Ferring; Other relationship: Alessa Therapeutics and Photocure; Research funding: AbbVie, Advantagene, Amgen, Aragon, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, Boston Scientific, CG Oncology, Clovis Oncology, Dendreon, DisperSol, Endocyte, Exact Imaging, Exelixis, Ferring, FKD Therapies, Forma Therapeutics, Foundation Medicine, Genentech, Guardant Health, InVitae, Istari Oncology, Janssen, Jiangsu Yahong Meditech, MDxHealth, Medivation, Merck, MT Group, Myovant, Myriad Genetics, Novartis, Nymox, OncoCellMDx, Oric Pharmaceuticals, Pacific Edge, Palette Life Sciences, Pfizer, Plexxikon, Point Biopharma, Propella Therapeutics, RhoVac, Sanofi, Seattle Genetics, Sesen Bio, Steba, Theralase, Tolmar, Urogen, Urotronic, US Biotest, Vaxiion, Veru, and Zenflow.
Maha Hussain: Consulting or advisory roles: Bayer, BMS, Janssen, Merck, Novartis, Pfizer, and Tempus; Patents, royalties, and other intellectual property: Dual inhibition of MET and VEGF for the treatment of castration resistant prostate cancer and osteoblastic bone metastases. Applicant/Proprietor Exelexis, Inc. Application No/Patent No. 11764665.4-1464 Application No/Pat; TITLE: METHOD OF TREATING CANCER Docket No: Serial Number: 224990/10-016P2/311733 61/481/671 Application Filed on: 5/2/2011; TITLE: SYSTEMS AND METHODS FOR TISSUE IMAGING, 3676 Our File: Serial Number: UM-14437/US-1/PRO 60/923,385 UM-14437/US-2/ORD 12/101,753; Honoraria: Astellas, AstraZeneca, Merck, OncLive, Precisca, Research to Practice, and UroToday; Research funding to institution: Arvinas, AstraZeneca, Bayer, Genentech, PCCTC, and Pfizer.
Fred Saad: Consulting or advisory roles: AbbVie, Advanced Accelerator Applications, Astellas, AstraZeneca/MedImmune, Bayer, Janssen, Knight, Myovant, Novartis, Pfizer, and Sanofi; Honoraria: AbbVie, Advanced Accelerator Applications, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Janssen, Knight, Merck, Myovant, Novartis, Pfizer, and Sanofi; Research funding to institution: Advanced Accelerator Applications, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Janssen, Merck, Novartis, Pfizer, and Sanofi.
Karim Fizazi: Consulting or advisory roles: Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Clovis, ESSA, Janssen, Novartis, Orion, Pfizer, and Sanofi; Travel, accommodation, and expenses: AstraZeneca, Janssen, and MSD; Honoraria (to institution): Astellas, Bayer, Janssen, and Sanofi.
Cora N. Sternberg: Consulting or advisory roles: Amgen, Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Clovis Oncology, Immunomedics now Gilead, Impact Therapeutics, Merck KGA, MSD, Pfizer, Roche/Genentech, Sanofi-Genzyme, Janssen, Lilly, Seattle Genetics, Foundation Medicine, Medscape, and UroToday.
E. David Crawford: Employment and leadership role (immediate family member): Blue Earth Diagnostics; Consulting or advisory roles: Bayer, Janssen, MdxHealth, Pfizer/Astellas, and Tolmar. Speaker bureaus: Bayer.
Bertrand Tombal: Honoraria: Amgen, Astellas, Bayer, Ferring, Janssen, Myovant, Pfizer, Sanofi; Consulting or advisory roles: Astellas, Bayer, Ferring, Janssen, Myovant, Pfizer/Astellas, Sanofi, Steba, and Takeda; Speaker bureaus: Amgen, Astellas, and Janssen; Research funding: Ferring; Expert testimony: Steba; Travel, accommodation, and expenses: Amgen, Astellas, Bayer, Ferring, Janssen, and Sanofi.
Luke T. Nordquist: Nothing to disclose.
Michael Cookson: Myovant Sciences, Merck & Company, and MDX Health.
Frank Verholen, Jay Jhaveri, and Shankar Srinivasan: Employees of Bayer.
Matthew R. Smith: Consulting or advisory roles: Amgen, Astellas, Bayer, Janssen, Lilly, Novartis, and Pfizer; Research funding to institution: Bayer, ESSA, Janssen, Lilly, and ORIC.
Author Contributions
Conception/design: N.D.S., M.H., F.S., K.F., C.N.S., E.D.C., B.T., F.V., J.J., S.S., M.R.S. Provision of study material or patients: N.D.S., M.H., F.S., K.F., C.N.S., E.D.C., B.T., L.N., M.R.S. Collection and/or assembly of data: N.D.S., M.H., F.S., K.F., C.N.S., E.D.C., B.T., S.S., M.R.S. Data analysis and interpretation: N.D.S., M.H., F.S., K.F., C.N.S., E.D.C., B.T., F.V., J.J., S.S., M.R.S. Manuscript writing: N.D.S., M.H., F.S., K.F., C.N.S., E.D.C., B.T., F.V., J.J., S.S., M.R.S. Final approval of manuscript: All authors.
Data Availability
Availability of the data underlying this publication will be determined according to Bayer’s commitment to the EFPIA/PhRMA “Principles for responsible clinical trial data sharing.” This pertains to scope, timepoint, and process of data access. As such, Bayer commits to sharing upon request from qualified scientific and medical researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the United States (US) and European Union (EU) as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 1, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct further research that can help advance medical science or improve patient care. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal. Data access will be granted to anonymized patient-level data, protocols and clinical study reports after approval by an independent scientific review panel. Bayer is not involved in the decisions made by the independent review panel. Bayer will take all necessary measures to ensure that patient privacy is safeguarded.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Availability of the data underlying this publication will be determined according to Bayer’s commitment to the EFPIA/PhRMA “Principles for responsible clinical trial data sharing.” This pertains to scope, timepoint, and process of data access. As such, Bayer commits to sharing upon request from qualified scientific and medical researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the United States (US) and European Union (EU) as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 1, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct further research that can help advance medical science or improve patient care. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal. Data access will be granted to anonymized patient-level data, protocols and clinical study reports after approval by an independent scientific review panel. Bayer is not involved in the decisions made by the independent review panel. Bayer will take all necessary measures to ensure that patient privacy is safeguarded.