Jamie Cesanek

Findings from the PEACE-1 trial published in the 

showed that adding abiraterone acetate (Zytiga) and prednisone to androgen-deprivation therapy (ADT) and docetaxel improved overall survival (OS) and radiographic progression-free survival rPFS in patients with de novo metastatic castration-sensitive prostate cancer (mCSPC).

In the phase 3 trial (NCT01957436), researchers randomized 1173 men with de novo mCSPC (57% high-volume and 43% low-volume) to receive standard of care (SOC) – which was ADT continuously with or without 75 mg/m

/3w for 6 cycles docetaxel (n = 296), SOC plus 1000 mg per day of abiraterone plus 5 mg twice daily of prednisone (n = 292), SOC plus 74 grades of radiotherapy to the primary tumor (RXT) (n = 293), or SOC plus abiraterone plus RXT (n = 292).

Trial candidates included men with de novo mCSPC who may have received up to 3 months of ADT before randomization for the study. The stratification factors were ECOG performance status (PS) (0 vs 1-2), site of metastasis (lymph node vs bone vs visceral), type of castration (orchidectomy vs LHRH-agonist vs LHRH-antagonist), and the use of docetaxel.

Patient characteristics were well-balanced between arms, as expected in such a large trial. Specifically regarding the 710 men who received ADT plus docetaxel as their SOC, about two-thirds of them had high metastatic burden – with 63% in the SOC +/- RXT + abiraterone arm (n = 355) and 65% in the SOC +/- RXT arm (n = 355).

Other notable characteristics included a median age of 66 in both arms, an ECOG PS score of 0 in most patients (70% and 69%, respectively), and 1-2 in the remaining (30% and 31%, respectively). Median time from diagnosis was 2.2 (IQR, 1.6-3.0) in the SOC +/- RXT + abiraterone arm and 2.2 (IQR, 1.4-2.9) in the SOC +/- RXT arm. Most patients in both arms had metastasis in the bone without visceral – 81% in the SOC +/- RXT + abiraterone arm and 79% in the SOC +/- RXT arm – while 8% of both arms had it in the lymph nodes, and 12% and 13%, respectively, had visceral metastasis.

The co-primary endpoints were rPFS and OS, and “PEACE-1 used a factorial design…answering 2 questions: the role of abiraterone and that of radiotherapy on top of SOC. The number of events for the abiraterone analysis has been reached, while a longer follow-up is needed to assess the role of radiotherapy,” according to the authors.

The co-primary endpoint of rPFS was reached in the ADT plus docetaxel (+/- RXT) population (HR, 0.50; 95% CI, 0.40-0.62; 

<.0001). It reduced the risk of radiographic progression or death by a median of 4.5 years with abiraterone, compared with 2 years without. Men with low- (HR, 0.58; 95% CI, 0.39-0.87; 

 <.006) and high-volume (HR, 0.47; 95% CI, 0.36-0.60; 

 <.0001) disease alike saw benefit with abiraterone.

Median follow-up in the overall population was 4.4 years, 5.7 in the ADT alone +/- RXT arm, and 3.8 in the ADT + docetaxel +/- RXT arm. OS was improved with abiraterone in the overall population (HR, 0.83; 95% CI, 0.69-0.99; 

 = .034) as well as in the ADT + docetaxel population (HR, 0.75; 95% CI, 0.59-0.96; 

For patients with high metastatic burden, adding abiraterone to ADT plus docetaxel reduced the risk of death by 28%. However, for men with low-volume disease, the medians have not yet been reached in either arm.

In terms of adverse events – which were generally balanced between arms – there were grade 3-5 events in more than 5% of patients in the ADT plus docetaxel population. These included neutropenic fever (5% vs 5%), neutropenia (10% vs 9%), liver toxicity (6% vs 1%), and hypertension (21% vs 13%) in the abiraterone and control arms, respectively.

When previously presenting the PEACE-1 findings at the 2021 ESMO Annual Congress, lead study author Karim Fizazi, MD, PhD, medical oncologist at Gustave Roussy and professor of Oncology at the University of Paris-Saclay in Villejuif, France, said, “We believe data are practice-changing. At the least, men with de novo high volume metastatic prostate cancer should be offered ADT plus docetaxel plus abiraterone based on evidence that this treatment combination will provide 2.5 years additional time without radiographic progression or death, and 1.5 additional years of survival.”

1. Fizazi K, Foulon S, Carles J, et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 x 2 factorial design. 

. Published online April 8, 2022. doi: https://doi.org/10.1016/S0140-6736(22)00367-1

Articles

Findings from the PEACE-1 trial published in the Lancet showed that adding abiraterone acetate and prednisone to androgen-deprivation therapy and docetaxel improved overall survival in patients with de novo metastatic castration-sensitive prostate cancer.

Abiraterone-based triplet boosts survival in de novo mCSPC

A recent analysis of data demonstrated that there were no major differences between health-related quality of life (HRQOL) in patients who received robotic-assisted radical cystectomy (RARC) when compared with patients who received open radical cystectomy (ORC). These results were evident in findings presented at the 2021 Society of Urologic Oncology Annual Meeting.

“This study is limited by a small sample size and the fact that it only includes a subset of the overall randomized control trial patients, therefore potentially introducing selection bias,” said Matthew B. Clements, MD, a urologic oncology fellow at Memorial Sloan Kettering Cancer Center, in a presentation of the data. “However, we feel that this study could reasonably exclude a large signal for differences based on operative approach and included a broad variety of quality of life domains.”

The study aimed to compare the 2 cystectomy types—RARC and ORC—over a broader range in a two-year period, due to the fact that previous studies had short postoperative follow-ups of 3-6 months and looked at limited quality of life domains.

To examine this broader range, the researchers analyzed patients with non-metastatic bladder cancer at Memorial Sloan Kettering Cancer Center who received a cystectomy. They focused on a randomized controlled trial comparing RARC and ORC with an open urinary diversion performed in both arms, as well as a prospective study of HRQOL that collected 14 patient-reported outcome measures. These measures were reported at baseline as well as 3-, 6-, 12-, 18-, and 24-months post-RC.

Additionally, longitudinal quality of life was compared in linear mixed-effect models adjusting for baseline scores as well as interaction for study arm by time over 24-months post-op.

Among 118 patients in the randomized controlled trial, 88 participated in the prospective HRQOL study. After excluding for ineligibility, researchers analyzed 72 patients (n = 32 for RARC and n = 40 for ORC).

They found that clinical characteristics between the two arms were generally balanced, but those who received RARC were more likely to be married or partnered and less likely to have received prior pelvic surgery.

There were no major differences in effect based on time of follow-up (aside from social functioning, among which scores were higher in ORC at 12 and 18 months but lower at 24 months [

 = .057]); pain, fatigue, appetite, abdominal symptoms (

 = .2), or bowel and psychosocial domains. There was higher sexual functioning with patients receiving ORC not meeting traditional significance (

 = .055). Body image was similar between groups (

 = .6), as well as urinary symptoms and incontinence (

 >.5), although some patients with ORC had evidence of lower early symptoms (

“These results are hypothesis-generating for larger studies that are needed comparing the approaches, which should also evaluate intracorporeal urinary diversion,” Clements concluded.

1. Clements, M; Atkinson, T; Dalbagni, G; et al. Health-Related Quality of Life After Robotic-Assisted vs Open Radical Cystectomy: Analysis of a Randomized Trial. Presented at Society of Urologic Oncology 22nd Annual Meeting; Virtual. November 30-December 3, 2021. Abstract 174.

A study examining a broader range of domains among patients receiving cystectomy found a large signal of differences in health-related quality of life.

Study results rule out any significant QOL differences after robotic vs open RC, further research needed to confirm results

While low-grade upper tract urothelial carcinoma (LG-UTUC)—generally considered low-risk—is commonly associated with recurrence in the bladder, development of metastatic disease and cancer-related mortality are both rare after a patient’s disease is managed with radical nephroureterectomy (RNU). Smoking and large tumor size are independently associated with early recurrence within 6 months of RNU.

The study, which was presented at the Society of Urologic Oncology 22nd Annual Meeting, aimed to describe recurrence patterns and identify predictive risk factors for recurrence after RNU to inform better surveillance strategies for clinicians after their patients receive RNU for LG-UTUC.

“Risk factors for timing and patterns of bladder and contralateral upper tract recurrence as well as development of metastatic disease after definitive management remain poorly described due to the overall low prevalence of the disease,” said Heather L. Huelster, MD, a 4th-year resident at Vanderbilt University Medical Center, during a presentation of the data.

To achieve their findings, investigators performed a retrospective electronic medical record review of 214 RNUs between February 2010 and April 2017. They identified 37 patients with LG-UTUC and excluded those with high-grade UTUC, evidence of nodal or distant metastatic disease, and pre-treatment with systemic therapy. Risk factors for early recurrence of urothelial malignancy (defined as recurrence within 6 months of RNU) were examined, and researchers obtained clinical, pathologic, recurrence, and survival data.

The mean age at surgery was 71.9 years. Most patients were male (74.8%), White (89.2%), and current or former smokers (83.8%), while less than half (40.5%) had history of urothelial carcinoma of the bladder. The median overall survival was 91.3 months, and 54.1% of patients had experienced recurrence over the course of 43.5 months.

Tumor size and multifocality were both associated with early recurrence, while analysis of demographics, surgical factors, and tumor characteristics showed that current smoking (OR, 10.6; 

 = .03) and increasing tumor size (OR, 1.9; 

 = .03) were independently associated with early recurrence.

“Current national and international guidelines vary with regard to use of risk stratification and their recommendation of timing of bladder surveillance after nephroureterectomy, citing low level evidence or weak categorization,” Huelster said.

She added that the data supports that large multi-focal tumors or low-grade tumors resected in patients who are current smokers bring a higher risk of early bladder recurrence. This may warrant more frequent cystoscopy at 3 to 6 months post-RNU, while patients without these risk factors may undergo annual cystoscopies.

“Additionally, initial urothelial recurrences are extremely rare more than 2 years after nephroureterectomy, so it may be reasonable to reduce the duration of cystoscopic surveillance, presenting an opportunity to reduce costs and patient burden associated with this,” Huelster said.

1. Huelster, H; Bilotta, A; Russo, N; et al. Predictive Risk Factors for Early Recurrence After Radical Nephroureterectomy for Low-Grade Upper Tract Urothelial Carcinoma. Presented at Society of Urologic Oncology 22nd Annual Meeting; Virtual. November 30-December 3, 2021. Abstract 117.

Recurrence is commonly associated with low-grade upper tract urothelial carcinoma and may be predicted by smoking status and tumor size.

Current smoking, large tumor size may predict early recurrence after radical nephroureterectomy in patients with low-grade UTUC

Findings from the PEACE-1 trial presented at the 2021 ESMO Annual Congress suggest adding abiraterone acetate (Zytiga) and prednisone to androgen-deprivation therapy (ADT) and docetaxel may be the new standard of care for the treatment of patients with de novo metastatic castration-sensitive prostate cancer (mCSPC).

“We believe [these] data [are] practice-changing,” said Karim Fizazi, MD, PhD, medical oncologist at Gustave Roussy and professor of Oncology at the University of Paris-Saclay in Villejuif, France, during a presentation of the findings. “At least, men with de novo high volume metastatic prostate cancer should be offered ADT plus docetaxel plus abiraterone based on evidence that this treatment combination will provide 2.5 years additional time without radiographic progression or death, and 1.5 additional years of survival.”

In the phase III trial (NCT01957436), researchers randomized 1173 men with de novo mCSPC (57% high-volume and 43% low-volume) to receive standard of care (SOC) – which was ADT continuously with or without 75 mg/m

“(Patient characteristics) were well-balanced between arms, as expected in such a large trial,” Fizazi explained. Focusing on the 710 men who received ADT plus docetaxel as their SOC, he added that about two thirds of them had high metastatic burden – with 63% in the SOC +/- RXT + abiraterone arm (n = 355) and 65% in the SOC +/- RXT arm (n = 355).

The co-primary endpoints were rPFS and OS, and “PEACE-1 used a factorial design, … answering 2 questions: the role of abiraterone and that of radiotherapy on top of SOC. The number of events for the abiraterone analysis has been reached, while a longer follow-up is needed to assess the role of radiotherapy,” Fizazi said.

The co-primary endpoint of rPFS was reached in the ADT plus docetaxel (+/- RXT) population (HR, 0.50, 95% CI, 0.40-0.62; 

<.0001). It reduced the risk of radiographic progression or death by a median of 4.5 years with abiraterone, compared with 2 years without. Men with low- (HR: 0.58, 95% CI, 0.39-0.87; 

 <.006) and high-volume (HR, 0.47, 95% CI, 0.36-0.60; p<0.0001) disease alike saw benefit with abiraterone.

Median follow-up in the overall population was 4.4 years, 5.7 in the ADT alone +/- RXT arm, and 3.8 in the ADT + docetaxel +/- RXT arm. OS was improved with abiraterone in the overall population (HR, 0.83, 95% CI, 0.69-0.99, p=0.034) as well as in the ADT + docetaxel population (HR, 0.75, 95% CI, 0.59-0.96, p=0.021).

“Reporting data about treatments use beyond progression is important,” Fizazi said, explaining that in the control arm, 84% of men who experienced cancer progression received at least 1 life prolonging therapy, and 81% received at least 1 next generation hormonal agent, mostly abiraterone or enzalutamide. “This clearly suggests that early use of these agents is better than deferred use.”

“We showed today that using … a treatment combination of ADT, docetaxel, and abiraterone further prolongs survival, with medians now reaching more than five years,” Fizazi said.

Determining the best way to combine systemic treatments with local radiotherapy, particularly in patients with oligo-metastatic disease, requires longer follow-up of PEACE-1.

1. Fizazi K, Charles Galceran J, Foulon S, et al. A phase III trial with a 2x2 factorial design in men with de novel metastatic castration-sensitive prostate cancer: overall survival with abiraterone acetate plus prednisone in PEACE-1. Presented at: 2021 ESMO Annual Congress. September 16-21, 2021.

Adding abiraterone acetate and prednisone to androgen-deprivation therapy and docetaxel may be the new standard of care for the treatment of patients with de novo metastatic castration-sensitive prostate cancer.

Jamie Cesanek

Articles

Abiraterone-based triplet boosts survival in de novo mCSPC

Study results rule out any significant QOL differences after robotic vs open RC, further research needed to confirm results

Current smoking, large tumor size may predict early recurrence after radical nephroureterectomy in patients with low-grade UTUC

Adding abiraterone to ADT/docetaxel may be new standard in de novo mCSPC