Dr. Mary Samplaski discusses online resources regarding male infertility.

Speaking of Urology Podcast 

Adding apalutamide (Erleada) to abiraterone acetate (Zytiga) and prednisone did not improve overall survival versus abiraterone/prednisone alone in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC), according to results from the phase 3 ACIS study.

Janssen Pharmaceutical (Johnson & Johnson), the developer of apalutamide, reported in a press release that it will no longer be pursuing regulatory approval of the novel treatment regimen.

“Safety results from ACIS were consistent with prior studies of Erleada and Zytiga plus prednisone, with no new safety signals observed. The study also generated valuable scientific outcomes and insights in subgroups of patients with luminal type in PAM50 test and tumors with average or high androgen receptor activity (molecular signatures of hormone sensitivity), which warrant further investigation,” Kiran Patel, MD, vice president, Clinical Development, Solid Tumors, Janssen Research & Development, stated in the press release.

“These data will be important in informing future programs in our pipeline, as we look to build upon our leadership and commitment in bringing transformational therapies to patients diagnosed with prostate cancer,” added Patel.

Overall survival was a secondary end point of the ACIS trial; the final results for the primary end point of radiographic progression-free survival (rPFS) were previously reported at the 2021 Genitourinary Cancers Symposium.

 The results showed that adding apalutamide to abiraterone and prednisone reduced the risk of radiographic progression or death by 30% in patients with chemotherapy-naïve mCRPC.

At a median follow-up of 54.8 months, the median rPFS was 24 months with the addition of apalutamide compared with 16.6 months with placebo plus abiraterone and prednisone (HR, 0.70). The data sustained the rPFS benefit with apalutamide observed at the primary efficacy analysis conducted at a median follow-up of 25.7 months: 22.6 months with apalutamide versus 16.6 months in the control arm (HR, 0.69; 

The double-blind phase 3 ACIS study included 982 patients with chemotherapy-naïve mCRPC who received ADT. Baseline characteristics were well balanced between the 2 treatment arms. Overall, the median patient age was 71 years, about 53% of patients had a Gleason score >7, the median PSA level was about 32 ng/mL, and all patients had an ECOG performance status of 0 (68%) or 1 (32%).

Patients were randomized 1:1 to apalutamide (n = 492) or placebo (n = 490) plus abiraterone and prednisone. All patients remained on continuous ADT. Patient randomization occurred between December 10, 2014, and August 30, 2016.

At the final rPFS analysis, 79.5% of patients in the apalutamide/abiraterone arm had a PSA decline ≥50% compared with 72.9% in the control arm (

 = .015). Also, 24.6% versus 19.2% of the 2 arms, respectively, had undetectable PSA (<0.2 ng/mL) at any time during treatment (

 = .040). However, the improved PSA decline with the apalutamide/abiraterone combo did not translate into a significant benefit in median time to PSA progression at 13.8 months versus 12 months in the control arm (

The time to initiation of cytotoxic chemotherapy was 36.1 months versus 34.2 months, respectively (

= .509). The times to chronic opioid use and pain progression were 47 months versus 53.3 months (

 = .500) and 21.8 months versus 26.5 months (

Regarding toxicity, no new safety signals were reported compared with previous reported studies of apalutamide. About two-thirds (63.3%) of patients in the apalutamide arm experienced treatment-emergent adverse events (TEAEs), compared with 56.2% of patients in the control group.

Several grade 3/4 TEAEs were more common in the apalutamide/abiraterone combination arm compared with the control arm: hypertension (20.6% vs 12.5%), fatigue (4.7% vs 3.9%), cardiac disorders (9% vs 5.7%), fall (3.3% vs 0.6%), skin rash (4.5 percent vs. 0.4 percent), seizures (0.2% vs 0), and fractures and osteoporosis (4.1% vs 1.4%).

The androgen receptor inhibitor apalutamide is currently approved by the FDA for the treatment of patients with nonmetastatic CRPC and metastatic castration-sensitive prostate cancer. The CYP17 inhibitor abiraterone has FDA-approved indications for use in combination with prednisone in patients with metastatic CRPC and metastatic high-risk castration-sensitive prostate cancer.

1. Janssen Provides Update on Phase 3 ACIS Study in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with ERLEADA® (apalutamide) and ZYTIGA® (abiraterone acetate) Plus Prednisone Combination. Published online April 20, 2021. Accessed April 20, 2021. https://bit.ly/3sAuVnG

2. Rathkopf DE, Efstathiou E, Attard G, et al. Final results from ACIS, a randomized, placebo (PBO)-controlled double-blind phase 3 study of apalutamide (APA) and abiraterone acetate plus prednisone (AAP) versus AAP in patients (pts) with chemo-naive metastatic castration-resistant prostate cancer (mCRPC). 

. 2021;39(suppl 6):9. doi: 10.1200/JCO.2021.39.6_suppl.9

Articles

The novel combination of apalutamide plus abiraterone and prednisone had previously met the primary end point of radiographic progression-free survival in the phase 3 ACIS trial. 

Apalutamide plus abiraterone does not improve survival in mCRPC

Findings from a study of incidental brain metastases in patients with metastatic renal cell carcinoma (mRCC) suggest that baseline brain imaging should be considered in most patients with metastatic kidney cancer.

The retrospective analysis, which was conducted by researchers at Gustave Roussy and Memorial Sloan Kettering Cancer Center (MSK), found that 4% of patients with mRCC had asymptomatic brain metastases.

"With 4% overall incidence in this cohort, one might conclude that baseline brain imaging should be considered in all patients with metastatic kidney cancer, particularly those with multiorgan involvement and/or pulmonary metastases," lead MSK researcher Ritesh R. Kotecha, MD, stated in a press release.

The retrospective analysis included patients with mRCC evaluated between 2001 and 2019 for clinical trial participation at Gustave Roussy and MSK who had received brain imaging during the evaluation, even though there was not clinical suspicion of brain involvement.

Overall, the analysis included 1689 patients enrolled across 68 trials. At a median follow-up of 14.1 months, 72 (4.3%) patients were identified as harboring occult brain metastases. The risk status was favorable, intermediate, and poor in 26%, 61%, and 13%, of patients, respectively, based on the International Metastatic RCC Database Consortium risk status scale. Further, 2 or more extracranial sites of disease were identified in 86% of patients; this included 92% of patients having lung metastases.

"Brain imaging is routinely obtained for kidney cancer patients with symptoms that suggest CNS metastases, but none of the patients with brain metastases included here were symptomatic," senior researcher Martin H. Voss, MD, also with MSK, stated in the press release. "In current practice, chest, abdomen, and pelvis are routinely imaged from the time that metastatic disease is first detected, yet many [clinicians] do not image the brain."

In 40% of the patients, the largest brain metastasis was more than 1 cm in diameter, and CNS involvement was multifocal in 38.5% of patients. Almost all patients (93%) received localized brain-directed therapy, which mainly consisted of radiotherapy.

The median overall survival (OS) was 10.3 months, with a 1-year OS probability of 48%. The investigators did not observe a correlation between OS and IMDC risk, number of lesions, or size of lesions.

“The retrospective study by Kotecha et al demonstrates that incidental brain metastases occur in a clinically significant percentage of patients with newly diagnosed metastatic renal cell carcinoma," Eric Jonasch, MD, professor, Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, who was not involved in this research, commented in the press release.

"The findings in this study are important for two reasons. First, they show that the overall prognosis of patients with brain metastases is consistently worse than the broader population of patients with metastatic renal cell carcinoma. We need to develop a deeper scientific understanding of why this patient population has a worse outcome, and we need to include them in future clinical trials. Second, they underscore the utility for MRI imaging of all patients with metastatic renal cell carcinoma both at initial diagnosis, and at regular intervals, to detect occult brain metastases, since specific treatment strategies are required for this patient population,” added Jonasch.

1. Kotecha RR, Flippot R, Nortman T, et al. Prognosis of incidental brain metastases in patients with advanced renal cell carcinoma. 

. 2021;19(4):432-438. doi: 10.6004/jnccn.2020.7634

2. JNCCN Study: Important Potential Role for Routine Brain Imaging in Advanced Kidney Cancer. Published online April 13, 2021. Accessed April 19, 2021. https://prn.to/3xgXBWL.

"Brain imaging is routinely obtained for kidney cancer patients with symptoms that suggest CNS metastases, but none of the patients with brain metastases included here were symptomatic," said Martin H. Voss, MD.

Study supports routine brain imaging at baseline in metastatic kidney cancer

explains how young physicians can create a habit of delaying gratification that could predispose them to burnout in the future. Pruthi is professor and chair of urology, University of California, San Francisco.

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“I think one of the issues that we face as physicians…is during training, long hours and a lack of control over our schedule indoctrinates surgeons with habits that may be counterproductive to achieving life balance after entering practice,” says Raj S. Pruthi, MD, MHA FACS.

What factors drive burnout among health care providers?

The FDA has granted priority review to 2 supplemental Biologics License Applications (sBLAs) for enfortumab vedotin-ejfv (Padcev) for use in patients with locally advanced or metastatic urothelial carcinoma, according to Seagen and Astellas Pharma, the developers of the antibody-drug conjugate.

One sBLA is intended to convert the drug’s accelerated approval in this setting to a full approval. The current approval is for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have received prior treatment with a PD-1/PD-L1 inhibitor and platinum-containing chemotherapy. The second sBLA seeks to expand this approval to include patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor and are ineligible for cisplatin.

The application for conversion to a full approval is based on results from the confirmatory phase 3 EV-301 trial, which were shared during the 2021 Genitourinary (GU) Cancers Symposium.

 In the study, enfortumab vedotin reduced the risk of death by 30% versus chemotherapy in patients with heavily pretreated locally advanced or metastatic urothelial carcinoma.

The sBLA for the expanded indication is based on data from cohort 2 of the phase 2 EV-201 trial,

 in which enfortumab vedotin was administered to cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior anti–PD-1/PD-L1 therapy. The confirmed objective response rate (ORR) in these patients was 52%, including a 20% complete response rate. Responses were observed across all prespecified subgroups, including patients with primary tumor sites in the upper tract (ORR = 61%), with liver metastasis (ORR = 48%), and those who did not respond to prior PD-1/PD-L1 inhibitors (ORR = 48%).

The FDA is scheduled to make a decision on these sBLAs on or before August 17, 2021.

"With our recent regulatory submissions, we intend to provide the highest level of clinical evidence supporting Padcev use—overall survival data from a randomized phase 3 trial—and expand availability in multiple countries where there is unmet medical need," said Andrew Krivoshik, MD, PhD, senior vice president and oncology therapeutic area head, Astellas, stated in a press release.

The open-label, randomized EV-301 trial (NCT03474107) included 608 patients with histologically or cytologically confirmed urothelial cancer, including patients with squamous differentiation or mixed cell types, were enrolled in the study and randomized 1:1 with stratification to either the enfortumab vedotin (n = 301) arm or the chemotherapy arm (n = 307).

Eligible patients had radiographic progression or relapsed during or after immune checkpoint inhibition for the treatment of advanced urothelial cancer and had received prior platinum-containing chemotherapy; patients also had an ECOG performance status of 0 or 1. Stratification variables included ECOG performance status (0 or 1), region of the world, and the presence or absence of liver metastasis.

Baseline characteristics were balanced between the 2 arms. The median age was 68 years and more than three-fourths of patients were male. Only 14% of patients were from the United States, 60% had an ECOG performance status of 1, two-thirds had a Bellmunt risk score of 0 or 1, 31% had liver metastases, and 87% had 1 or 2 prior lines of therapy. In the enfortumab vedotin arm, 20% responded to prior immune checkpoint inhibition and 16% responded in the chemotherapy arm.

The median OS with enfortumab vedotin was 12.88 months versus 8.97 months with chemotherapy, which translated to a 30% reduction in the risk of death (HR, 0.70; 

= .00142). Subgroup analyses for OS favored the enfortumab vedotin arm for all groups excepts female patients (HR, 1.17).

Median PFS with enfortumab vedotin was 5.55 months versus 3.71 months with chemotherapy (HR, 0.62; 

Confirmed ORR in the enfortumab vedotin arm was 40.6%, which included CRs in 4.9%, and the disease control rate (DCR) was 71.9%. In the chemotherapy arm, the ORR was 17.9% with CRs in 2.7%, and a DCR of 53.4% (

Treatment-related adverse event (TRAE) rates were similar between the 2 arms, with any-TRAE rates of 94% in the investigational arm and 92% in the control arm, and grade ≥3 TRAE rates of 51% and 50%, respectively. Serious TRAEs were reported in 23% of patients in each arm and TRAEs led to treatment discontinuation in 14% of patients in the enfortumab vedotin arm and 11% in the chemotherapy arm.

The single-arm, phase 2 EV-201 trial examined enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer who had been previously treated with a PD-1/PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (cohort 1) and those who have not received a platinum-containing chemotherapy and who are ineligible for cisplatin (cohort 2).

Data for cohort 1 of the trial (n = 128) supported the accelerated approval of enfortumab vedotin. In these patients, the antibody-drug conjugate elicited an ORR of 44%, which included a 12% CR rate, and a 32% partial response rate.

The results for cohort 2, on which the sBLA for expanded is based, included 89 patients. Baseline characteristics showed that patients were a median age of 75, male (74%), and 15% were obese. Two-thirds (67%) of patients exhibited a moderate decrease in kidney function. Looking at the primary site of tumor, 43% had a tumor in the upper tract.

The median time to response was 1.81 months with some patients who have durable responses that extend beyond a year or more. Median DOR was 10.9 months. At a median follow-up of 13.4 months, the median PFS was 5.8 months and median OS was 14.7 months.

In terms of safety, any grade overall TRAEs occurred in 97% of patients and grade 3 or higher TRAEs occurred in 55% of patients. TRAEs led to discontinuations in 16% of patients, and peripheral sensory neuropathy was the most common in 4%. There were 4 deaths that were considered to be treatment related by the investigator and these were a result of acute kidney injury, metabolic acidosis, multiple organ dysfunction syndrome, and pneumonitis.

1. Seagen and Astellas Announce Submission of Two Supplemental Biologics License Applications to the U.S. FDA for PADCEV® (enfortumab vedotin-ejfv) in Locally Advanced or Metastatic Urothelial Cancer. Published April 19, 2021. Accessed April 19, 2021. https://prn.to/3ed3VWh. 2. Powles T, Rosenberg JE, Sonpavde G, et al. Primary results of EV-301: A phase III trial of enfortumab vedotin versus chemotherapy in patients with previously treated locally advanced or metastatic urothelial carcinoma. 

2021;39(suppl 6):393. doi:10.1200/JCO.2021.39.6_suppl.393

3. Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma. Published online February 12, 2021. 

4. Balar AV, McGregor BA, Rosenberg JE, et al. EV-201 Cohort 2: Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors. J Clin Oncol. 2021;39(suppl 6).394. doi: 10.1200/JCO.2021.39.6_suppl.394

The applications are supported by data from the EV-301 and EV-201 trials.

FDA grants 2 enfortumab vedotin applications priority review in urothelial carcinoma

Matthew D. Galsky, MD, interprets the results from the final overall survival (OS) analysis of the IMvigor130 trial, which were shared during the 2021 American Association for Cancer Research Virtual Annual Meeting. The IMvigor130 trial randomized patients with metastatic urothelial carcinoma to atezolizumab plus platinum/gemcitabine; atezolizumab alone; or placebo plus platinum/gemcitabine.

Galsky says that the final OS analysis comparing atezolizumab/chemo versus placebo/chemo did not show a statistically significant OS benefit with atezolizumab, and thus, OS follow-up remains ongoing. Galsky also discusses the finding from an exploratory analysis which suggest that outcomes with atezolizumab/chemo might be affected by the specific platinum regimen used.

Galsky is professor of Medicine; director of Genitourinary Medical Oncology; director of the Novel Therapeutics Unit; and co-director of the Center of Excellence for Bladder Cancer at the Tisch Cancer Institute and the Icahn School of Medicine at Mount Sinai.

Galsky highlights final OS data from the IMvigor130 trial, along with an exploratory analysis examining outcomes by type of chemotherapy used. 

Dr. Matthew Galsky interprets latest atezolizumab/chemo results in bladder cancer

Karen Nash is a medical reporter and media consultant based in Monroeville, PA.

 reached out to 3 urologists (selected randomly) and asked them each the following question: What is your impression of virtual meetings and conferences?

“I haven’t attended virtual conferences; however, our department at [the University of California] Irvine does all our Grand Rounds on Zoom. They usually entail scientific lectures, with outside speakers 2 to 3 times a month.

The only meeting I commonly attend is the Western Section, but haven’t gone since returning to California.

In the past 2 years, I attended a billing conference and the Society of Academic Urologists [SAU annual meeting]. I wouldn’t have gone back to the billing conference so soon, anyway. The SAU went virtual in January, but my clinical schedule had started picking up, so I didn’t want to take time off. If we took time off when the [operating rooms] were opening up for elective procedures, I’d have felt bad about time away from patients, even if we weren’t traveling to attend.

Virtual speakers are good and bad. They serve their purpose—we’re able to look at slides, hear the speaker, take notes on our computer. That’s a convenience I definitely like.

We were actually doing Zoom lectures prior to the pandemic because it’s a way to get nationally known figures to give lectures without having to travel across country for a 1-hour presentation. Obviously, it’s a technique a lot of departments have picked up since COVID-19 to keep the quality up and keep lectures going.

My main complaint about virtual lectures is the loss of camaraderie of seeing colleagues face to face and having casual conversations.

I expect we’ll continue to see a hybrid system in that there will be in-person as well as Zoom lectures.”

“I didn’t participate in virtual conferences this year, although I’ve done a ton of virtual meetings, speaker trainings, advisory boards, but not 1 [continuing medical education] or AUA [American Urological Association] meeting. I’m one of the senior physicians in our organization and have both clinical and system-level responsibilities. When COVID-19 hit, my responsibilities grew. I’m also cochair of our new system-wide Cancer Center of Excellence.

We did most hospital-system meetings virtually. After the pandemic, I hope we incorporate that into our operation because Houston is a very spread-out city—54 miles across—and we have 13 hospitals. When we had a system meeting, we’d have it centrally and everybody had to drive there. But attendance at virtual meetings is through the roof because everybody participates. Even if they’re in the [operating room], between cases they go to the doctors’ lounge and sign in. People are actively engaged in the discussion. Sitting in their office, people don’t feel threatened chiming in and giving an opinion. Meetings also start and end on time because we’re not waiting for stragglers. I would find it deleterious to eliminate them after the pandemic.

AUA meetings could become a hybrid for a couple reasons, [such as] revenues involved for the convention centers, the hotels, and vendors. Secondly, certain things can be harder to do virtually. Vendors find it harder to demonstrate their products.

On the other hand, we had a list of big group courses and some were at the same time. They can video everything, so later you watch whatever courses you missed.”

“I just attended the Society for Benign Prostatic Disease [virtual meeting], and maybe a bit of 1 or 2 AUA [American Urological Association] meetings.

It’s a good way to access the general content, probably easier than being there in person, in some ways. For a plenary session or something, it’s just as good, if not better, to do it virtually—having the slide right in front of you while you’re sitting at a desk. It’s easier to take notes on your computer and to look things up while you’re watching.

I certainly miss interacting with colleagues, talking to people about new ideas and new practices. The industry portions are less useful virtually than in-person where we can walk around the booths and see new products and talk to people from the companies.

In smaller breakout and poster sessions that have more Q&A, you get less out of them virtually.

Post pandemic, I would like to see a return to in-person meetings. They’re more engaging overall. Being able to interact with your colleagues is better in person. Portions of the meetings could be done virtually in a very effective manner, which might help with the space considerations. They might have combination meetings where some content is virtual, and some is in person.

I think they’ll offer content virtually for people who might not be able to travel easily for logistical reasons having nothing to do with the pandemic. People who can’t go to every meeting but would still like access the content.”

"My main complaint about virtual lectures is the loss of camaraderie of seeing colleagues face to face and having casual conversations," says one urologist.

3 urologists share their impression of virtual meetings and conferences

Cheryl Guttman Krader is a contributor to Dermatology Times, Ophthalmology Times, and Urology Times.

Findings from a systematic review and meta-analysis of urosepsis after ureteroscopy (URS) for stone management show that this serious complication occurs at an unexpectedly high rate and is associated with some surprising risk factors, according to investigators.

The research, which is the first systematic review with meta-analysis to specifically investigate risk factors for and incidence of urosepsis after URS, analyzed data from 13 studies that included 5597 patients.1 It found a 5% pooled incidence of postoperative urosepsis and determined that preoperative stent placement, positive preoperative urine culture, older age, diabetes, longer procedure time, and ischemic heart disease were each associated with a statistically significant increased risk.

“Ureteroscopy has become the leading approach for treating stone disease because of its efficacy and the perception that it is a very safe procedure and associated with minimal morbidity. Therefore, the 5% rate of urosepsis was surprising to us and to other urologists as well, judging from posted tweets,” lead author Naeem Bhojani, MD, told 

Bhojani and senior author Ben H. Chew, MD, MSc, pointed out that although their study identified associations between certain variables and urosepsis risk, it does not establish causal relationships. For that reason and in the absence of evidence about the efficacy of preventive strategies targeting these factors, it is not possible to make any recommendations for risk management.

“Nevertheless, we believe our findings can be useful for urologists in preoperative risk stratification and for guiding the intensity of postoperative surveillance,” said Chew, an associate professor in the Department of Urologic Sciences at the University of British Columbia in Vancouver, Canada.

The 13 studies used for the meta-analysis included 5 prospective trials. Across the 13 studies, the rate of urosepsis ranged from 0.2% to 17.8%. The use of different criteria for urosepsis diagnosis and different durations of postoperative symptom surveillance (1 to 30 days) may, in part, account for the wide variability in rate, said Bhojani, a principal scientist, urologist, and associate professor at the University of Montreal in Canada.

Although surprisingly high, the 5% rate of urosepsis appears to be true. In a follow-up investigation, the investigators turned to the IBM MarketScan Commercial Database that contained information from over 110,000 URS procedures performed in the United States. In that large cohort of cases with prospectively collected data, they found a nearly identical 30-day postoperative sepsis rate of 4.91%.

Pre-op stent placement, older age were among risk factors

In the meta-analysis, preoperative stent placement, positive preoperative urine culture, and older age were the strongest risk factors for postoperative urosepsis. The effects of having a stent or a positive urine culture are easy to understand because patients with these findings are likely colonized with bacteria or have bacteriuria, Bhojani said.

The association with ischemic heart disease, however, was particularly surprising and hard to rationalize. Explanations for the associations between urosepsis and older age, diabetes, and longer procedure time are also unclear, although Bhojani postulated that increasing procedure time could favor translocation of bacteria into the bloodstream because it would be accompanied by an increasing level of intrarenal pressure.

“There are some observational data suggesting that exposure to a longer duration of increased intrarenal pressure can lead to infection being transmitted into the bloodstream, and we are currently studying that relationship further,” Bhojani said.

Chew noted that large prospective studies would be needed to determine effective ways for reducing urosepsis risk.

“Based on our study, we cannot say that patients with the risk factors we identified should be given more powerful antibiotics as prophylaxis or kept in the hospital longer so that they can be watched more closely for postoperative sepsis,” he said. “However, we think that urologists should remain aware that patients with 1 or more of the risk factors warrant more intensive monitoring because they may be at significant risk for urosepsis after URS.”

1. Bhojani N, Miller LE, Bhattacharyya S, Cutone B, Chew BH. Risk factors for urosepsis after ureteroscopy for stone disease: a systematic review with meta-analysis. 

. Published online March 15, 2021. doi:10.1089/end.2020.1133

Review of nearly 5600 patients found a 5% pooled incidence of postoperative urosepsis.

Meta-analysis generates surprising insights on postureteroscopy urosepsis

“The patients who use statins had longer overall survival, longer prostate cancer-specific survival, and a trend towards longer time before they became castration resistant,” 

says in this podcast. Hamilton is an associate professor of urology at the University of Toronto.

Podcasts

Hamilton discusses findings from a recent study published in European Urology.

Dr. Robert J. Hamilton on statin use in men starting ADT for prostate cancer

The first patient has been diagnosed in the pivotal phase 3 ENLIGHTED trial exploring padeliporfin Immune Photo Activated Cancer Therapy (ImPACT) for the treatment of patients with low-grade upper tract urothelial cancer (UTUC), according to Steba Biotech, the developer of the investigational treatment.

The padeliporfin ImPACT platform involves the intravenous delivery and activation of the photosensitive drug padeliporfin. Once the drug is in the patient, it is “activated by a non-thermal light delivery system that uses a lower energy laser light channeled through optical fibers.”

 The minimally invasive approach enables targeted ablation of the tumor. The treatment was initially explored in prostate cancer and is now being investigated in UTUC and other solid tumors.

“The treatment of UTUC remains a clinical challenge with limited options available to effectively help our patients while avoiding the risk of significant morbidity. This study will work closely with investigators in the United States, Europe, and Israel with the goal of confirming the safety and efficacy of padeliporfin ImPACT as a promising new therapy for treating patients with urothelial cancers involving the upper urinary tract,” Jonathan Coleman, MD, principal investigator of ENLIGHTED and urologic surgeon at Memorial Sloan Kettering Cancer Center, stated in a press release.

The open-label, single-arm ENLIGHTED trial is enrolling patients with low-grade UTUC in either the ureter or the kidney. Treatment will comprise 2 phases, induction and maintenance. The target enrollment is 100 patients. Follow-up will last 1 to 5 years after treatment. The primary end point is the number of patients with absence of UTUC tumors in the entire ipsilateral calyces’ renal pelvis and ureter. This outcome measure will be assessed endoscopically. The investigators anticipate that data for the primary end point will be available in 2022.

Padeliporfin ImPACT previously received FDA Fast Track and Orphan Drug designations for the treatment of patients with UTUC. The designations are designed to expedite the review and development of novel treatments that will fill an unmet medical need.

Overall, about 6000 to 8000 new cases of low-grade UTUC occur annually in the United States. Despite some breakthroughs, there remains a high unmet need for novel UTUC treatments.

“The successful initiation of the pivotal trial for padeliporfin ImPACT is an important milestone in our ambitious new development program. Our aim is to unlock the potential of our novel oncology platform, padeliporfin ImPACT, on solid tumors with high unmet medical need. Targeting diseases such as UTUC, where surgery is either impossible or clinically undesirable could be very beneficial for patients living with these conditions. The ENLIGHTED trial is 1 of 2 clinical and 5 preclinical programs that we are advancing this year,” Dr. David Perry, head of Research and Development, Steba, stated in the press release.

1. Steba Biotech Treats First Patient in Pivotal ENLIGHTED Study of Padeliporfin ImPACT in Low Grade Upper Tract Urothelial Cancer. Published online April 20, 2020. Accessed April 20, 2020. https://bit.ly/3x9tHDF

2. Steba biotech. A Novel Treatment Path. Accessed March 8, 2021. https://www.stebabiotech.com/technology-innovation.

Padeliporfin ImPACT previously received FDA Fast Track and Orphan Drug designations for the treatment of patients with upper tract urothelial cancer. 

Phase 3 study launches of padeliporfin ImPACT for UTUC

 discuss physician social media use, covering topics such as advice for medical professionals just starting out on Twitter, how the platform can enhance scientific conference experiences, and how it can be used to aid in research. Loeb is Professor of Urology and Population Health at New York University and the Manhattan Veterans Affairs. She also hosts the Men's Health Show on Sirius XM satellite radio, and is the incoming Chair of the American Urological Association Public Media Committee. You can find her on Twitter @LoebStacy. Stork is Assistant Clinical Professor in the Department of Urology at the University of Michigan. He is also the current Chairperson for the Urology Care Foundation Public Education Council. He is active on Twitter @StorkBrian and has a long running blog on his website 

Loeb and Stork offer pointers for beginners and current users alike.

Dr. Robert J. Hamilton on statin use in men starting ADT for prostate cancer

Phase 3 study launches of padeliporfin ImPACT for UTUC

Dr. Stacy Loeb and Dr. Brian Stork discuss social media for physicians