Colleen Moretti

Combining radiotherapy with next-generation hormonal therapy is a feasible approach to explore in phase 3 trials enrolling patients with high-risk localized or locally advanced prostate cancer (HRLPC), according to an analysis of the phase 3 ATLAS trial shared during the 2022 ASCO Annual Meeting.

The current treatment approach for patients with HRLPC comprises androgen deprivation therapy (ADT) combined with radiotherapy (RT).

Although effective in some patients, ADT plus RT doesn’t significantly reduce the risk for metastases and death.

In the ATLAS trial, investigators are assessing if adding apalutamide (Erleada) to ADT (gonadotropin-releasing hormone agonist [GnRHa]) and external beam radiation therapy (EBRT) is feasible in patients with high-risk disease.

A total of 1,503 patients (median age, 67 years) are currently enrolled onto the trial. A total of 89% and 11% of patients have an ECOG PS of 0 or 1, respectively. In regard to tumor classification, 66% are high-risk and 34% are very high-risk. Median PSA is 6.3 ng/mL and cT2 in 44%, CT2 in 50% and cN1 in 13%.

“Baseline characteristics demonstrate high- and very higher-risk features of prostate cancer and pelvic nodal involvements in patients undergoing primary RT in clinical practice,” the researchers wrote.

In 90% of patients included in the study, RT use was standard EBRT to prostate/pelvis over 6-8 weeks (cumulative 78-81 GY); in 10% of patients recent hypofractionation schedules were applied, and 5.6% had EBRT combine with brachytherapy.

“The RT schedules applied reflect recent evidence and guideline changes for the use of hypofractionation in this patient population,” the researchers wrote.

Patients were randomized to APA or placebo plus GnRHa for 30 (28-d) treatment cycles. All patients received GnRHa and primary RT as standard of care. And the placebo group also received bicalutamide in the neoadjuvant setting, concurrent with RT.

The authors noted that the RT schedules in ATLAS mimic recent evidence and guideline changes for the use of hypofractionation in this group of patients.

1. Sandler H, Freedland S, Shore N, et al. Patient (pt) population and radiation therapy (RT) type in the long-term phase 3 double-blind, placebo (PBO)-controlled ATLAS study of apalutamide (APA) added to androgen deprivation therapy (ADT) in high-risk localized or locally advanced prostate cancer (HRLPC). J Clin Oncol. 2022; 40(suppl_16):5084. doi: 10.1200/JCO.2022.40.16_suppl.5084

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Combining radiotherapy with next-generation hormonal therapy is a feasible approach to explore in phase 3 trials enrolling patients with high-risk localized or locally advanced prostate cancer, according to an analysis of the phase 3 ATLAS trial.

Analysis: Feasible to explore RT plus next-gen hormonal therapy in phase 3 high-risk local prostate cancer trials

The rates of upgrading and adverse pathology at radical prostatectomy cancer are similar in Hispanic men and non-Hispanic men with prostate cancer, according to results presented at the 2021 Society of Urologic Oncology Annual Meeting.

“Hispanic (patients) are more negatively impacted by socioeconomic factors, such as neighborhood effects, compared (with White patients). However, despite this, they have similar survival compared with white (patients) suggesting an at least equal, if not more favorable, cancer characteristic,” said Helen Y. Hougen, MD, a urologic oncology fellow in the department of Urology at the University of Miami Miller School of Medicine.

Researchers sought to examine a rate and pattern of upgrading (any increase in Gleason grad [GG] from biopsy to prostatectomy) and adverse pathology (extraprostatic extension, seminal vesicle invasion, LN+) in Hispanic patients using an institutional prostatectomy database, specifically in the south Florida region.

Previously, the SEER database has demonstrated there are similar survival outcomes between Hispanic and White patients with prostate cancer; however, this database does not include South Florida, which has a high population of Hispanic men.

Patients included in the study were non-Hispanic White (NHW; n = 688), Hispanic White (HW; n = 736), and Black (n = 426) men who underwent a radical prostatectomy between 2014 to present. There was no significant difference in age, BMI, PSA, prostate size, or biopsy GG between groups.

Results demonstrated that 651 patients had upgrading, and it was not different between groups.

On the univariable analysis, patients who were Black had a lower rate of adverse pathology compared with patients who were White. Hougen explained this may be because the Black population in south Florida has a greater number of men who are of Caribbean decent, not African origin.

In the multivariable analysis, significant predictors for upgrading included older age, higher PSA, and lower prostate weight. And there were no differences observed between the three groups and the rate of upgrading.

Adverse pathology odds increased with older age, higher PSA, higher BMI, lower prostate weight, increased number of biopsy cores, and higher GG.

1. Hougen, H. Iakymenko, O, Punnen, S, et al. Race is not associate with prostate cancer upgrading in Hispanic men undergoing radical prostatectomy. Society of Urologic Oncology 22nd Annual Meeting; Virtual. December 1-3, 2021; Orlando, FL. Abstract 148.

The study included patients who were Hispanic and from the south Florida region, which was not included in previous studies. 

Race not linked to cancer upgrading in Hispanic men receiving radical prostatectomy

Patients with localized prostate cancer (PCa) and a BMI of at least 33 kg/m2 or greater were less likely to receive surgery (RP) as treatment, according to results presented at Society of Urologic Oncology 22nd Annual Meeting.1

Nathan Samora—who presented the results and is a 4th year medical student at the Vanderbilt University School of Medicine—and fellow researchers sought to study the association between BMI and treatment modality as well as patient reported outcomes after therapy.

The researchers found that men who were younger, less-educated, Black or had more comorbidities were more likely to be obese (

 <0.001). Additionally, there was no significant difference in PCa risks across BMI groups.

Results demonstrated a linear increase in the likelihood of receiving an RP as the BMI increased from 18 to 28 and there was a linear decrease of receiving an RP thereafter. This became statistically significant at a BMI of greater than or equal to 33, Samora said. At no BMI was the likelihood of receiving active surveillance (AS) statistically significant.

Additionally, it was found that obese men have worse sexual function at baseline and all other time points throughout the 5 years; however, it was observed that trajectories between normal weight and overweight men are highly similar.

After adjusting for disease specifications between obese and non-obese men, it was found that there were not clinically important differences in patient reported outcomes for men who underwent definitive treatment.

Results also demonstrated that men who were obese and on active surveillance had worse urinary incontinence compared to non-obese peers at 6 months and through the 5 years.

Patients (n = 2378) included were from the Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) Study and were mostly white (77%), with a median age of 64 years and a median BMI of 27 kg/m2. Patient-reported quality of life was measured at enrollment and 6, 12, 36, and 60 months using the 26-item Expanded Prostate Index Composite (EPIC-26).

1. Samora, N, Wallis, C, Tallman, J, et al. Association between BMI and Localized Prostate Cancer Treatment Modality and Patient-Reported Outcomes. Presented at Society of Urologic Oncology 22nd Annual Meeting; Virtual. November 30-December 3, 2021. Abstract 105. 

Men who were obese and on active surveillance had worse urinary incontinence compared to non-obese peers through 5 years. 

BMI in patients with localized prostate cancer may predict likelihood of receiving treatment, quality of life

Phase 1b/2 data shared during the 2021 ESMO Congress showed promising clinical activity with the novel agent sabizabulin (VERU-111) in patients with metastatic castration-resistant prostate cancer (mCRPC).

Both phases of the study involved patients who were previously treated with at least 1 androgen receptor-targeted therapy. The aim of the study was to evaluate the safety, maximum-tolerated dose, and efficacy of sabizabulin.

Patients included in the study were advanced in their treatment, Mark C. Markowski, MD, PhD, medical oncologist from John Hopkins University in Baltimore, Maryland, highlighted during his presentation. Many patients had previously been treated with abiraterone acetate (Zytiga), enzalutamide (Xtandi), a combination of both, or apalutamide (Erleada) or proxalutamide.

The phase 1b portion used a 3+3 design in 39 patients (median age, 74 years). Initially, each dose was administered orally on days 1-7 on a regimen of every 21 days. If this regimen was well tolerated and considered safe, the frequency was increased to a daily dosing on days 1-14 every 21 days. And if that was tolerated, patients then advanced to dosing daily until disease progression or toxicity.

In the phase 1b portion of the study, 10 patients reached at least 4 cycles of continuous dosing. Of that 10, 6 had any PSA response, 2 had at least a 50% PSA response. Additionally, two patients had a partial response, with the remaining 8 achieving stable disease. The median radiographic progression-free survival (rPFS) was greater than 12 months (range, 6.0-28+ months). And as of August 2021, 2 of the 10 patients remained on the study.

“That’s the most mature data we have. (It’s) a bit difficult given our dose escalation strategy,” Markowski noted.

The open-label phase 2 portion of the study comprised 44 patients (median age, 73 years) and evaluated the recommended dose of 63 milligrams (mg) daily. “We found that (the) recommended phase 2 dose was 63 milligrams per day, so daily dosing was safe and feasible,” Markowski explained.

The most common adverse events among 54 patients included diarrhea, fatigue, ALT and AST increases, all of which were mostly grade 1 and 2. Markowski added that there were no reports of clinically relevant neutropenia or neurotoxicity, “which we’ve seen before with taxane chemotherapy.”

Objective response rate in the intention-to-treat population (n = 26) was 20.7%, with 5 partial responses and 1 complete response. And in evaluable patients who qualified for a future phase 3 trial (n = 26) it was 23.1%.

In patients that received at least 63 mg (n = 55) median rPFS is estimated to be at least 7.4 months.

Markowski detailed that a phase 3 trial, known as VERACITY (NCT04844749), is currently underway and is evaluating 32 mg of sabizabulin for the treatment of mCRPC against an alternative AR-targeting agent. Patients in this study had prior treatment with 1 AR-targeted therapy, and no chemotherapy. This trial has a primary endpoint of rPFS.

1. Markowski M, Eisenberger M, Tutrone R, et al. Sabizabulin, an oral cytoskeleton disruptor, to treat men with metastatic castration resistant prostate cancer who failed an androgen receptor targeting agent. Presented at 2021 ESMO Congress; September 16-21, 2021; virtual. 578MO.

Sabizabulin was well tolerated and associated with significant and durable objective tumor responses in patients with metastatic castration resistant prostate cancer.

Colleen Moretti

Articles

Analysis: Feasible to explore RT plus next-gen hormonal therapy in phase 3 high-risk local prostate cancer trials

Race not linked to cancer upgrading in Hispanic men receiving radical prostatectomy

BMI in patients with localized prostate cancer may predict likelihood of receiving treatment, quality of life

Sabizabulin emerges as novel option in mCRPC