Kristi Rosa

Advanced prostate cancer treatment with the oral gonadotropin-releasing hormone receptor (GnRH) antagonist relugolix (Orgovyx) was associated with an acceptable toxicity profile with favorable tolerability, according to findings from a recent study.

The results, derived from a detailed safety analysis of the pivotal phase 3 HERO trial (NCT03085095), were presented at the 2022 American Urological Association Annual Meeting.

A lower percentage of patients who received relugolix experienced major adverse cardiovascular events (MACE) compared with those who were given leuprolide (Lupron), at 2.9% and 6.2%, respectively. Specifically, Kaplan-Meier estimates of incidence rate revealed a risk reduction of 54% with relugolix (HR, 0.46; 95% CI, 0.24-0.88).

Notably, in a subset of men who had a reported medical history of cardiovascular events, MACE rates on study drug treatment in the investigative and control arms were 3.6% and 17.8%, respectively; this translated to 5.8-fold higher odds of experiencing MACE with leuprolide vs relugolix.

“Relugolix, an oral nonpeptide GnRH receptor antagonist, was generally well tolerated in the phase 3 HERO study,” lead study author Bryan Mehlhaff, MD, of the Oregon Urology Institute, and colleagues, wrote in a poster on the data. “Adverse effects [AEs] occur with varying time of onset and duration depending on the type of event.”

HERO enrolled patients with histologically or cytologically confirmed adenocarcinoma of the prostate that needed at least 1 year of continuous androgen deprivation therapy.

 To be eligible for enrollment, patients needed to be at least 18 years of age, and have 1 of the following 3 clinical presentations: evidence of biochemical or clinical relapse after local primary intervention with curative intent, newly diagnosed hormone-sensitive metastatic disease, or advanced localized disease that is not likely to be cured by local primary intervention with curative intent.

If patients experienced MACE within 6 months of study start, they were excluded.

Study participants were randomized 2:1 to receive oral relugolix at a once-daily dose of 120 mg following a single loading dose of 360 mg, or leuprolide injections given every 12 weeks for 48 weeks. Stratification factors included geographic region, the presence or absence of metastatic disease, and age.

The primary end point of the trial was sustained castration rate, and key secondary end points included noninferiority of relugolix to leuprolide with regard to sustained castration rate with a noninferiority margin of -10 percentage points.

Other end points included cumulative probability of testosterone suppression to less than 50 ng/dL on day 4 and 15, the percentage of patients with a prostate-specific antigen (PSA) response at day 15 with confirmation at day 29, the profound castration rate on day 15, and the FSH level at the end of week 24. 

In December 2020, the FDA approved relugolix for use in patients with advanced prostate cancer

based on earlier findings from HERO.3 Data showed that 96.7% (95% CI, 94.9-97.9) of those who received relugolix (n = 622) maintained castration through 48 weeks vs 88.8% (95% CI, 84.6%-91.8%) of those who were given leuprolide (n = 308); the difference of 7.9 percentage points (95% CI, 4.1-11.8) was indicative of noninferiority and superiority of relugolix.

Notably, all secondary end points showed superiority with relugolix over leuprolide (

< .001). The cumulative probability of castration on day 4 with relugolix was 56.0% vs 0% with leuprolide; on day 15, these rates were 98.7% and 12.0%, respectively. Moreover, the cumulative probability of testosterone suppression to profound castrate levels on day 15 was 78.4% with relugolix and 1.0% with leuprolide. More patients in the investigative arm had a confirmed PSA response at day 15 vs those in the control arm, at 79.4% and 19.8%, respectively (

Updated data from the HERO trial shared at the 2021 AUA Annual Meeting showed that relugolix did not significantly delay onset of castration resistance vs leuoprolide.

 At 48 weeks, the castration resistance–free survival (CRFS) rate was 74.3% (95% CI, 68.6%-79.2%) with relugolix vs 75.3% (95% CI, 66.7%-81.9%) with leuprolide in the metastatic disease cohort (n = 434; HR, 1.03; 95% CI, 0.68-1.57; 

= .84). Similar CRFS rates were reported in the modified intention-to-treat population (n = 1074).

At this year’s meeting, investigators shared a review of the safety findings from the trial, including an analysis of toxicity onset and duration. The safety population was comprised of 622 patients who received relugolix and 308 patients who were given leuprolide.

Data indicated that 92.9% of those in the investigative arm and 93.5% of those in the control arm experienced AEs. The AEs that occurred in more than 10% of patients in the relugolix and leuprolide arms, respectively, included hot flash (54.3% vs 51.6%), fatigue (21.5% vs 18.5%), constipation (12.2% vs 9.7%), diarrhea (12.2% vs 6.8%), and arthralgia (12.1% vs 9.1%).

Grade 3 or higher toxicities were experienced by 18.0% of those in the relugolix arm vs 20.5% of those in the leuprolide arm. Grade 3 or higher AEs reported in 1% or more of patients in the investigative and control arms, respectively, comprised hypertension (1.6% vs 0.6%), diabetes (1.0% vs 0.6%), and syncope (1.0% vs 1.0%). All other grade 3 or higher toxicities were reported with comparable incidence in both arms.

For the toxicities that were experienced by more than 10% of patients, the median time to onset ranging from 19.0 days to 142.0 days in the investigative arm and 41.0 days to 188.5 days in the control arm. The duration of these effects varied.

Notably, diarrhea was noted to have a short median duration compared with other toxicities; this AE had a median duration of 9 days (range, 1-370) in the relugolix arm vs 3 days (range, 1-224) in the leuprolide arm. Fatigue and hot flash were found to be more persistent. The median duration of fatigue in those who received relugolix was 289 days (range, 2-429) vs 274 days (range, 3-426) in those who were given leuprolide. Moreover, hot flash lasted for a median of 342 days (range, 15-477) with relugolix vs 331 days (range, 1-428) with leuprolide.

Regarding MACE, the median time to onset with relugolix was 177 days (range, 38-343) vs 132 days (range, 8-352) with leuprolide.

“MACE appeared to occur earlier and with a higher percentage in leuprolide vs relugolix groups, possibly supporting a different risk/mechanism between GnRH agonists and antagonists,” the study authors concluded.

1. Mehlhaff B, Shore ND, George DJ, et al. Oral relugolix for androgen deprivation therapy in advanced prostate cancer: detailed safety analysis from the randomized phase 3 HERO study. Presented at: 2022 American Urology Association Annual Meeting; May 13-16, 2022; New Orleans, LA. Abstract MP27-16.

2. Shore ND, Saad F, Cookson MS, et al. Oral relugolix for androgen-deprivation therapy in advanced prostate cancer. 

. 2020;382(23):2187-2196. doi:10.1056/NEJMoa20043253.

3. FDA approves first oral hormone therapy for treating advanced prostate cancer. News release. FDA. December 18, 2020. Accessed May 14, 2022. http://bit.ly/2Ws5nvz

4. Saad F, George DJ, Cookson MS, et al. Relugolix vs leuprolide effects on castration resistance-free survival from the phase 3 HERO study in men with advanced prostate cancer. Presented at: 2021 American Urological Association Annual Meeting; September 10-13, 2021; virtual. Abstract MP24-07.

Articles

“Relugolix, an oral nonpeptide GnRH receptor antagonist, was generally well tolerated in the phase 3 HERO study,” wrote Bryan Mehlhaff, MD, and coauthors.

Acceptable toxicity profile is seen with relugolix in advanced prostate cancer

Results from the phase 2 BAYOU trial showed that adding olaparib (Lynparza) to frontline durvalumab (Imfinzi) did not lead to a significant progression-free survival (PFS) benefit in patients with platinum-ineligible metastatic urothelial carcinoma; however, the combination may boost PFS in patients harboring homologous recombination repair (HRR) mutations.

The BAYOU trial (NCT03459846) data, which were presented during the 2022 Genitourinary Cancers Symposium, showed that the median investigator-assessed PFS with the doublet (n = 78) in the intent-to-treat (ITT) population was 4.2 months (95% CI, 3.6-5.6) vs 3.5 months (95% CI, 1.9-5.1) with durvalumab alone (n = 76; HR, 0.94; 95% CI, 0.64-1.39; log-rank 

However, data from a prespecified secondary analysis suggested that olaparib plus durvalumab had a potential PFS benefit in a subgroup of patients with homologous recombination repair (HRR) mutations. In this population, the median PFS achieved with the doublet (n = 17) was 5.6 months (95% CI, 1.9-8.1) vs 1.8 months (95% CI, 1.7-2.2) with single-agent durvalumab (n = 14; HR, 0.18; 95% CI, 0.06-0.47; log-rank 

“The PFS results suggest a potential role for PARP inhibitors in the treatment of metastatic urothelial carcinoma with HRR mutations, and further investigation is warranted,” Jonathan E. Rosenberg, MD, chief of the Genitourinary Oncology Service in the Division of Solid Tumor Oncology, and Enno W. Ercklentz Chair at Memorial Sloan Kettering Cancer Center, said in an oral presentation on the data.

Patients with metastatic urothelial carcinoma are known to have a poor prognosis, particularly those who cannot tolerate platinum-based chemotherapy, Rosenberg said. For these patients, atezolizumab (Tecentriq) and pembrolizumab (Keytruda) are given, irrespective of PD-L1 status; however, a high unmet need for additional therapeutic options remains.

Defects in DNA damage repair occur in approximately 24% of patients with urothelial carcinoma, and the dysregulation of DNA repair genes has been associated with poorer outcomes. Notably, these defects are known to make cancer cells sensitive to PARP inhibitors. As such, investigators hypothesized that HRR mutations and PARP inhibition could strengthen the antitumor response achieved with immune checkpoint inhibitors.

To this end, BAYOU sought to enroll approximately 150 patients with unresectable, stage IV urothelial carcinoma, a transitional cell carcinoma of the bladder, renal pelvis, ureter, or urethra. Patients needed to be at least 18 years of age and have an ECOG performance status ranging from 0 to 2.

Study participants were randomized 1:1 to receive either intravenous (IV) durvalumab at a dose of 1500 mg every 4 weeks plus oral olaparib at a twice-daily dose of 300 mg or durvalumab alone. Key stratification factors included HRR status (mutant vs wild-type) and Bajorin risk index (0 vs 1 vs 2).

The primary end point of the trial was PFS by RECIST v1.1 criteria and per investigator assessment. Key secondary end points comprised PFS by RECIST v1.1 criteria in the subgroup of patients with HRR mutations, overall survival (OS), duration of response (DOR), objective response rate (ORR), and PFS at 6 months by RECIST v1.1 criteria in both the ITT population and the HRR-mutated subset. Other end points of interest included safety and tolerability.

The data cutoff date was October 15, 2020. The median follow-up in the investigative arm was 9.8 months (range, 0.0-29.0) vs 10.7 months (range, 1.0-29.0) in the control arm.

Those who received the doublet were slightly older than those who received durvalumab monotherapy, at a median of 79 years (range, 47-89) vs 72 years (range, 45-88). Slightly more than half of patients in both arms were male. In the investigative arm, 51% of patients were White, 49% were Asian, and none were Black or African American; in the control arm, these rates were 46%, 51%, and 3%, respectively.

Regarding ECOG performance status, 15% of patients who received olaparib plus durvalumab had a status of 0, 38% had a status of 1, and 44% had a status of 2. Of those who were given durvalumab monotherapy, 18% had an ECOG performance status of 0, 45% had a status of 1, and 37% had a status of 2. Most patients in both arms had pure transitional cell carcinoma.

Moreover, 67% of patients who received the doublet had visceral metastases, and 33% had lymph-node only disease; these rates were 63% and 37%, respectively, in those who received the monotherapy. In the investigative and control arms, 11.5% and 10.5% of patients, respectively, received previous therapy.

In the investigative arm, 21% of patients did not have any Bajorin risk factors, 49% had 1 risk factor, and 31% had 2. In the control arm, 24% did not have Bajorin risk factors, 47% had 1, and 29%, and 2. Seventy-eight percent of patients in the doublet arm had HRR wild-type disease, and 22% had HRR-mutated disease; in the control arm, these rates were 82% and 18%, respectively.

The 20 most frequent gene mutations demonstrated a pattern that proved to be consistent with what has previously been observed in bladder cancer, according to Rosenberg. Across all patients, the most common HRR gene mutations were loss of p53 function (59.5%) and TERT promoter mutations (55.6%).

Utilizing the validated FoundationOne assay, investigators tested tumor samples for loss of function alterations in the following 15 prespecified HRR genes: 

. HRR mutations were found in 7 of the 15 genes analyzed. The most frequent included 

, which was identified in 8.5% of all tumors and in 41.9% of patients in the HRR-mutated subset, as well as 

, which was found in 4.6% of all tumors and in 22.6% of those in the HRR-mutated subgroup.

Exploratory subgroup analyses also showed that PFS favored olaparib/durvalumab over durvalumab alone in those with a Bajorin risk index of 0 (HR, 0.42; 95% CI, 0.18-0.92). However, PFS appeared to favor single-agent durvalumab over the doublet in those with HRR wild-type disease (HR, 1.29; 95% CI, 0.85-1.96), in those with a Bajorin risk index of 1 (HR, 1.90; 95% CI, 1.07-3.49), and in those with a Bajorin risk index of 2 (HR, 1.19; 95% CI, 0.63-2.28).

Data from the prespecified secondary analysis of OS showed that olaparib plus durvalumab did not result in improved OS vs durvalumab monotherapy in the ITT population. Specifically, the median OS with the doublet 10.2 months (95% CI, 7.0-13.9) vs 10.7 months (95% CI, 7.2-17.3) with durvalumab alone (HR, 1.07; 95% CI, 0.72-1.61; log-rank 

The same was true in the subgroup of patients with HRR wild-type disease. The median OS with olaparib plus durvalumab (n = 61) was 10.9 months vs 13.7 months with single-agent durvalumab (n = 62; HR, 1.35; 95% CI, 0.85-2.16). However, the doublet (n = 17) was found improve median OS in the subset of patients with HRR-mutated disease vs the monotherapy (n = 14), at 8.6 months vs 5.8 months, respectively (HR, 0.56; 95% CI, 0.25-1.23).

The addition of olaparib to durvalumab resulted in an ORR of 28.2% in the ITT population vs 18.4% with durvalumab alone. In the investigative arm, 3.8% of patients achieved a complete response, 24.4% had a partial response (PR), 34.6% achieved stable disease (SD) for at least 7 weeks, 32.1% experienced disease progression, and 5.1% were not evaluable. The median DOR in the investigative arm was 8.9 months (range, 4.7-12.1) vs 14.8 months (range, 7.5-17.2) in the control arm.

In the HRR-mutated subset, the combination produced an ORR of 35.3% vs 0% with durvalumab alone. Among those who responded to the doublet, 35.3% achieved a PR and 29.4% had SD for 7 weeks or longer. Moreover, 29.4% had progressive disease and 5.9% were not evaluable. The median DOR with olaparib/durvalumab was 6.7 months (range, 3.7-12.0) in this subset.

No new safety signals were observed with the combination of olaparib and durvalumab, according to Rosenberg. Any-grade treatment-related adverse effects were experienced by 72.4% of patients who received the doublet (n = 76) vs 60.5% of those given the monotherapy (n = 76).

The most common toxicities observed in the investigative arm included anemia (any grade, 23.7%; grade 3 or 4, 6.6%), nausea (any grade, 19.7%; grade 3 or 4, 1.3%), fatigue (any grade, 15.8%; grade 3 or 4, 1.3%), decreased appetite (any grade, 10.5%), diarrhea (any grade, 10.5%), and hypothyroidism (any grade, 9.2%). In the control arm, the most common toxicities included anemia (any grade, 13.2%; grade 3 or 4, 1.3%), pruritus (any grade, 10.5%), fatigue (any grade, 6.6%), rash (any grade, 5.3%), nausea (any grade, 3.9%), hypothyroidism (any grade, 3.9%).

One death was reported in the durvalumab monotherapy arm, and this was because of anemia.

1. Rosenberg JE, Park SH, Dao TV, et al. BAYOU: a phase II, randomized, multicenter, double-blind, study of durvalumab (D) in combination with olaparib (O) for the first-line treatment of platinum-ineligible patients with unresectable, stage IV urothelial carcinoma (UC). 

. 2022;40(suppl 6):437. doi:10.1200/JCO.2022.40.6_suppl.437.

BAYOU trial results showed no significant PFS boost in all-comer population with addition of olaparib to frontline durvalumab in metastatic urothelial carcinoma, but potential benefit for combo was observed in HRR-mutation–positive subgroup. 


Olaparib falls short as add-on to durvalumab in mUC, but combo may benefit HRR+ subgroup

Long-term data for UGN-101 (Jelmyto) showed that the mitomycin-containing reverse thermal gel induced a durable recurrence-free survival benefit in patients with low-grade upper tract urothelial carcinoma (LG-UTUC).

An analysis from the pivotal phase 3 OLYMPUS trial presented during the 2021 AUA Annual Meeting showed that as of March 4, 2021, the median duration of response (DOR) achieved with UGN-101 induction therapy was 28.1 months (95% CI, 14.6-37.1) in 15 evaluable patients. Eighty percent of patients (n = 12) experienced a durable response, defined as having no evidence of recurrence or not having to undergo radical nephroureterectomy.

Twenty percent of patients (n = 3) did not experience a durable response because of disease recurrence (13%; n = 2). One patient needed to undergo radical nephroureterectomy (7%); however, notably, this was performed because of ureteral stricture rather than disease recurrence.

Patients who experienced recurrence underwent endoscopic ablation. None of the patients with disease recurrence progressed to high-grade disease. At the time of the last follow-up, the disease-specific survival rate was 100%.

“UGN-101 demonstrates long-term durability that exceeds that achieved with kidney-sparing options like laser ablation,” said senior author of the trial Karim Chamie, MD, MSHS, an associate professor of Urology at the University of California, Los Angeles, in a presentation on the data. “With laser ablation therapies, we’ve seen [from] pooled analyses of prior publications the recurrence rates [were] more than 65% at a median follow-up of 43 months.”

LG-UTUC is a rare disease for which limited therapeutic options are available. Despite significant progress made with endoscopic therapies, most patients still need to undergo radical nephroureterectomy, according to Chamie, who added that data from population-level analyses indicate that up to 70% of patients with low-grade, noninvasive disease still undergo more extirpative surgery.

Advances made with endoscopic surgeries have yielded several kidney-sparing benefits. However, results from a pooled analysis of 597 patients, 78% of whom had low- or intermediate-grade disease, demonstrated that 65% of the population experienced disease recurrence following ureteroscopic therapy at a median follow-up of 43 months (range, 24-58).

 “That is quite significant,” Chamie noted.

As such, investigators launched the phase 3 OLYMPUS trial (NCT02793128) to evaluate UGN-101. Earlier results from the study resulted in the April 2020 FDA approval of the mitomycin gel for the treatment of patients with LG-UTUC.

 The previously reported estimated the a durability of response rate of 84% at 12 months in those who achieved a complete response (CR) after UGN-101 induction treatment.

The open-label, single-arm, phase 3 trial enrolled a total of 71 patients with LG-UTUC who had never undergone treatment or who had recurrent low-grade, noninvasive disease with at least 1 measurable papillary tumor.

Study participants received UGN-101 once a week for the duration of 6 weeks followed by a 4- to 6-week grace period, according to Chamie. In this period, patients were assessed for the primary efficacy end point of CR rate at their primary disease evaluation (PDE) visit. If patients experienced a CR to treatment, they went on to receive the gel monthly for up to 11 additional months.

“Patients were determined to have a CR if ureteroscopy and cytology were entirely normal,” Chamie explained. “If there were any abnormalities, patients underwent a biopsy by which this was determined to be either recurrence or a CR.”

A key secondary end point of the trial was durable response at the 12-month follow-up visit, and other end points included durability of response with UGN-101 at 3, 6, and 9 months following the PDE visit. As part of the long-term follow-up, investigators examined duration of response, disease recurrence, disease progression, and death.

The primary analysis of the trial was done on the intention-to-treat (ITT) population, which comprised patients who were given 1 or more instillation of the gel. Secondary analyses were conducted in patients who achieved a CR at the time of their PDE visit, and long-term follow-up analyses looked at those who had a CR at 12 months following their PDE visit.

Of the 71 patients enrolled to the study (ITT population), 10 discontinued UGN-101 (9 because of adverse effects [AEs] and 1 because of withdrawn consent), and 19 did not achieve a CR by their PDE visit. A total of 42 patients in the ITT population experienced a CR to treatment at the time of their PDE visit, which translated to a CR rate of 59.2% (95% CI, 46.8%-70.7%). Of these patients, 1 withdrew consent, 10 discontinued treatment, and 8 experienced disease recurrence.

Twenty-three patients maintained their CR at 12 months, translating to a CR rate of 56.1% (95% CI, 39.7%-71.5%). Five of these patients were at sites where follow-up protocol was not yet initiated, 2 did not have data available, and 1 was lost to follow-up. At the 2021 AUA Annual Meeting, Chamie shared data on the remaining 15 evaluable patients.

Limitations of the study included a small sample size and missing data for 8 of 23 patients who had durable responses at 12 months following their PDE visit, Chamie concluded.

1. Kleinman N, Pierorazio P, Raman JD, et al. Long-term recurrence-free survival following UGN-101 treatment for low-grade upper tract urothelial carcinoma. Presented at: 2021 American Urological Association Annual Meeting; September 10-13, 2021; virtual. Abstract LBA02-10.

2. Petros FG, Li R, Matin SF. Endoscopic approaches to upper tract urothelial carcinoma. 

. 2018;45(2):267-286. doi:10.1016/j.ucl.2017.12.009

3. FDA approves first therapy for treatment of low-grade upper tract urothelial cancer. News release. FDA. April 15, 2020. Accessed September 13, 2021. https://bit.ly/3liG6jn.

The mitomycin-containing reverse thermal gel UGN-101 (Jelmyto) produced durable responses in patients with low-grade upper tract urothelial carcinoma.

UGN-101 shows long-term recurrence-free survival benefit in low-grade UTUC

A prognostic factor analysis identified multiple potential biomarkers for over survival (OS) outcomes with lutetium 177 (177Lu) in patients with metastatic castration-resistant prostate cancer (mCRPC).

Specifically, findings presented at the 2021 AUA Annual Meeting showed that both Cancer and Leukemia Group B (CALGB) prognostic risk group and the receipt of subsequent FDA-approved life-prolonging therapies were correlated with OS when 177Lu was administered in this patient population.

The overall median OS observed with 177Lu was 20.7 months in 125 patients with mCRPC who received treatment on sequential prospective clinical trials of the prostate-specific membrane antigen (PSMA)–targeted beta-emitting radionuclide. The median OS in those who received 177Lu-J591 (n = 76) was slightly longer, at 23.3 months. In those who received 177Lu-PSMA-617 (n = 49), the median OS was 16.7 months.

Factors linked with longer OS included CALGB prognostic score (28.1 months vs 16.9 months; 

<.0001), circulating tumor cell (CTC) decline (24.9 months vs 19.2 months; 

= .046), and receipt of subsequent therapy (28.1 months vs 14.8 months; 

Moreover, higher PSMA PET standardized uptake value (SUV; imaging score 4 vs 0 to 3) was linked with prolonged OS (18 months vs 10 months; 

= .015), and higher administered activity (22.1 months vs 18.6 months; 

= .074) and DNA damage repair (DDR) alterations (33.9 months vs 20.6 months; 

= .24) tended to be associated with longer OS.

“DDR mutations, higher administered radioactivity, higher PSMA PET SUV, and posttreatment [circulating tumor cell] count decline are promising biomarkers worthy of further exploration,” Scott Tagawa, MD, MS, FACP, study author, professor of medicine and urology at Weill Cornell Medicine, and an attending physician at NewYork-Presbyterian–Weill Cornell Medical Center, said in a poster presentation on the data.

PSMA-targeted radionuclide therapy represents a promising treatment for patients with advanced prostate cancer, Tagawa said. PSMA can be targeted using antibodies, such as J591, or small molecule ligands, like PSMA-617, labeled with 177Lu. However, optimal selection and effective biomarkers still need to be defined and established, Tagawa added.

To conduct the combined prognostic analysis presented during the meeting, investigators collected data from a total of 125 patients who received treatment with 177Lu on prospective PSMA-TRT clinical trials at a single institution between 2003 and 2020. To be included in the analysis, patients had to have completed treatment with the radionuclide therapy at least 1 year before the analysis.

Variables of interest included type of PSMA targeting, dose administered, comorbidities, CALGB prognostic risk group, PSMA imaging, CTC counts, known DDR alterations, and receipt of subsequent therapies. PSMA imaging was scored based on the maximum tumor uptake relative to the mean liver uptake on a scale that ranged from 0 to 4. Investigators utilized Cox regression analysis and the Kaplan-Meier method to examine the link between the variables and survival. The data cutoff for the combined analysis was March 2021.

Among the 125 patients included, the median PSA was 50.14 ng/dL (range, 0.66-2222.4) and the median age at treatment was 72 years (range, 48-93). Regarding Halabi risk category, 57.6% of patients had high risk, 37.6% had intermediate risk, and 4.8% had low risk. Additionally, 49.6% previously received taxane chemotherapy and 47.2% previously received abiraterone acetate (Zytiga)/enzalutamide (Erleada). Eighty percent of patients had metastasis in the lymph node, 24.8% in the liver, 24.8% in the lung, and 97.6% in the bone.

The median number of subsequent therapies received was 1 (range, 0-10), and these included abiraterone/enzalutamide (26.4%), docetaxel (32.8%), cabazitaxel (Jevtana; 18.4%), platinum chemotherapy (17.6%), radium-223 dichloride (Xofigo; 7.2%), sipuleucel-T (Provenge; 4.8%), and additional PSMA-TRT (11.2%).

Additional data from a multivariable analysis indicated that high Halabi risk group (HR, 1.78; 95% CI, 1.16-2.73; 

= .009) and total number of subsequent therapies (HR, 0.79; 95% CI, 0.71-0.89; 

<.001) retained their prognostic significance. Moreover, a trend for DDR mutations holding prognostic significance was observed (HR, 0.68; 95% CI, 0.34-1.36; 

1. Sun M, Thomas C, Ho B, et al. Long-term follow-up and prognostic factor analysis in men with metastatic castration-resistant prostate cancer (mCRPC) who receive prostate-specific membrane antigen (PSMA)-targeted lutetium-177 (177Lu). Presented at: 2021 American Urological Association Annual Meeting; September 10-13, 2021; virtual. Abstract MP24-05.

The prognostic factor analysis included patients who received either 177Lu-PSMA-617 or 177Lu-J591.

Kristi Rosa

Articles

Acceptable toxicity profile is seen with relugolix in advanced prostate cancer

Olaparib falls short as add-on to durvalumab in mUC, but combo may benefit HRR+ subgroup

UGN-101 shows long-term recurrence-free survival benefit in low-grade UTUC

Study highlights prognostic factors for Lutetium 177 in mCRPC