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Michael O. Koch, MD, is professor and chairman of the department of urology, Indiana University School of Medicine, Indianapolis.

Over the last 20 years, radical retropubic prostatectomy has evolvedto become the standard of care in men with localized prostate cancer. Becauseof the morbidity of this procedure, however, interest has grown in the developmentof non-surgical modalities. Unfortunately, many of these non-surgical approaches,such as monotherapy with radioactive seed implantation, have resulted indisappointing results or excessive morbidity, as in first-generation cryotherapy.

HIFU may offer advantages in PCa, but the jury is still out

The FDA has accepted a Biologics License Application (BLA) seeking approval of nivolumab (Opdivo) co-formulated with Halozyme’s proprietary recombinant human hyaluronidase (rHuPH20), or subcutaneous nivolumab, for the treatment of patients with all previously approved solid tumor indications for nivolumab as a monotherapy, monotherapy maintenance following completion of combination therapy with nivolumab plus ipilimumab (Yervoy), or in combination with chemotherapy or cabozantinib (Cabometyx).

Nivolumab is currently approved under several indications, including in combination with ipilimumab for the first-line treatment of patients with intermediate- or poor-risk advanced renal cell carcinoma (RCC), in combination with cabozantinib for the first-line treatment of patients with advanced RCC, for the treatment of patients with advanced RCC who have received prior anti-angiogenic therapy, and in combination with cisplatin and gemcitabine for the first-line treatment of patients with unresectable or metastatic urothelial carcinoma.

The FDA is set to have a decision regarding the subcutaneous nivolumab formulation on or by December 29, 2024.

 According to a news release from Bristol Myers Squibb,

 approval of the formulation would make it the first and only subcutaneously administered PD-1 inhibitor.

“We believe subcutaneous nivolumab has the potential to make a significant difference in the lives of patients, which is reinforced by the FDA’s acceptance of our application,” said Gina Fusaro, PhD, vice president, global program lead, Bristol Myers Squibb, in the news release.

 “Opdivo is a foundational PD-1 inhibitor approved for many different types of cancer, and our continued investment in research that puts patients first remains a priority. If approved by the FDA, the subcutaneous administration of nivolumab would provide patients and their physicians with a new option that delivers the same well-known benefits as IV Opdivo but with the improved convenience of an injection administered in 3 to 5 minutes rather than a 30-to-60-minute infusion.”

The BLA submission is supported by findings from the phase 3 CheckMate-67T trial (NCT04810078), in which subcutaneous nivolumab met the study’s co-primary end points by demonstrating noninferiority to intravenous (IV) nivolumab regarding time average nivolumab serum concentration over 28 days (C

; geometric mean ratio [GMR}, 2.098; 90% CI, 2.001-2.200) and minimum serum concentration at a steady state (C

Data from the study, which were presented at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco, California,

 also showed that subcutaneous nivolumab demonstrated noninferiority to IV nivolumab in the key powered secondary end point of objective response rate (ORR). Specifically, the subcutaneous arm demonstrated an ORR of 24.2% (95% CI, 19.0-30.0) per blinded independent central review (BICR), compared with 18.2% (95% CI, 13.6-23.6) in the IV arm.

The safety profile for subcutaneous nivolumab was consistent with that of the IV formulation. Among patients who received the subcutaneous formulation, 8.1% experienced injection-site reactions, with all being low-grade and transient. Deaths due to study drug toxicity occurred in 3 patients in the subcutaneous arm and 1 patient in the IV arm. Most deaths that occurred during the study were due to disease progression.

In total, the phase 3, open-label CheckMate-67T trial enrolled 495 patients with advanced or metastatic ccRCC who had received prior systemic therapy. Patients were randomly assigned 1:1 to receive 1200 mg subcutaneous nivolumab plus rHuPH20 every 4 weeks (n = 248) or to 3 mg/kg IV nivolumab every 2 weeks (n = 247) for up to 2 years of treatment or until disease progression, unacceptable toxicity, withdrawal, or death.

The co-primary pharmacokinetic end points for noninferiority testing were C

 of subcutaneous nivolumab vs IV nivolumab. The key secondary end point was ORR per BICR.

Final completion of the CheckMate-67T study is expected in January 2026.

1. U.S. Food and Drug Administration accepts Bristol Myers Squibb’s application for subcutaneous nivolumab (nivolumab and hyaluronidase). News release. Bristol Myers Squibb. May 6, 2024. Accessed May 7, 2024. https://news.bms.com/news/corporate-financial/2024/U.S.-Food-and-Drug-Administration-Accepts-Bristol-Myers-Squibbs-Application-for-Subcutaneous-Nivolumab-nivolumab-and-hyaluronidase/default.aspx

2. Bristol Myers Squibb announces updated action date by the U.S. Food and Drug Administration for subcutaneous nivolumab (nivolumab and hyaluronidase). News release. Published online and accessed May 21, 2024. https://investors.bms.com/iframes/press-releases/press-release-details/2024/Bristol-Myers-Squibb-Announces-Updated-Action-Date-by-the-U.S.-Food-and-Drug-Administration-for-Subcutaneous-Nivolumab-nivolumab-and-hyaluronidase/default.aspx

3. George S, Bourlon TB, Chacon MR, et al. Subcutaneous nivolumab (NIVO SC) vs intravenous nivolumab (NIVO IV) in patients with previously treated advanced or metastatic clear cell renal cell carcinoma (ccRCC): Pharmacokinetics (PK), efficacy, and safety results from CheckMate 67T. 

4. A study of subcutaneous nivolumab versus intravenous nivolumab in participants with previously treated clear cell renal cell carcinoma that is advanced or has spread (CheckMate-67T). ClinicalTrials.gov. Last updated March 1, 2024. Accessed May 7, 2024. https://clinicaltrials.gov/study/NCT04810078

The FDA is set to have a decision regarding the subcutaneous nivolumab formulation on or by December 29, 2024. 

News

FDA accepts BLA for subcutaneous nivolumab in solid tumors

Dr. Ziho Lee discusses a course from this year's World Congress of Endourology and Uro-Technology

Expert recaps urologic reconstruction course from WCET 2024

describes a course from this year's World Congress of Endourology and Uro-Technology. Lee is an assistant professor of urology and the director of Urologic Male Reconstruction and Robotic Reconstructive Surgery in the department of urology at Northwestern University Feinberg School of Medicine in Chicago, Illinois.

I think one of the highlights for me was getting the opportunity to teach a course on robotic reconstruction at the World Congress of Endourology [and Uro-Technology]. And what I really enjoy about these courses is it really brings together urologists from many different backgrounds and many different nationalities to come together and discuss the latest treatment options and advances in the care that we provide our patients. Because I think in medicine, it's absolutely critical to be collaborative and work with other physicians, to share ideas and really improve upon whatever techniques are available. Because when we all come together and work together, we can really improve surgeries for our patients, not just locally, but from a global level. And so I had the opportunity to participate in a course on robotic ureteral reconstruction. The course was directed by Dr Wilson Chan, who is the president of the Hong Kong Society of Endourology, Dr David Duchene from the University of Kansas, and Dr Benjamin Waldorf from UT Chattanooga. We really focused on 3 aspects of ureteral reconstruction. Dr Duchene gave excellent tips and tricks on distal ureteral reconstruction involving primary reimplantation, Psoas hitch, and Boari flaps. Then, Dr Benjamin Waldorf gave an excellent tips-and-tricks session on buccal mucosa graft ureteroplasty. I think that technique has really revolutionized how ureteral reconstruction is performed and the ability to take on extremely challenging cases, and so that was an incredible lecture and teaching session. And then I gave some of my tips and tricks in patient selection for robotic ileal replacement, and also in bladder augmentation. I just want to underscore how important and how incredible it was to participate in this, because there was a lot of dialogue among the faculty and also the course participants. And it was great for me personally, because I got to learn on how I can improve my surgeries for my patients, and then also share some of my tips and tricks. And so I feel like it was a very collaborative environment that was really beneficial for all those involved.

"I just want to underscore how important and how incredible it was to participate in this, because there was a lot of dialogue among the faculty and also the course participants," says Ziho Lee, MD.

Break Wave Lithotripsy appears to be safe and effective in the treatment of patients with urolithiasis, according to data from a first-in-human, prospective, international clinical trial (NCT03811171) presented at the 2024 World Congress of Endourology and Uro-Technology in Seoul, South Korea.

“While not all stones are accessible or treatable with Break Wave lithotripsy, the ones that are amenable to treatment are the ones that are able to be localized with ultrasound: ureterovesical junction, distal ureter, proximal ureter, UPJ, mid and lower pole stones, and some upper pole stones that are not obscured by lung," said presenting author Ben H. Chew, MD, MSc, FRCSC, of the University of British Columbia, in correspondence with 

. "The treatment for these patients is much easier than typical shockwave lithotripsy as they are not required to fast or undergo sedation or anesthesia. This will potentially change how we deal with acute kidney stones since we can now treat patients at the point of care (in the clinic or the ER) with no anesthesia with results that are similar to shockwave lithotripsy.”

In total, the trial included 44 patients, with 59% presenting with renal stones and 41% presenting with stones in the distal ureter. Patients included in the trial underwent Break Wave Lithotripsy for 30 minutes at varying dose levels up to 8 MPa of acoustic pressure.

Data showed that any stone fragmentation was achieved in 88% of patients. Of those, 70% of patients had fragments of 4 mm or smaller, 55% had fragments of 2 mm or smaller, and 49% of patients were completely stone free on CT imaging. Among all patients, 7% required retreatment with either shock wave lithotripsy or ureteroscopy.

The optimal dose setting was identified and administered to 36 of 44 patients in the trial. Among those patients, 92% achieved any stone fragmentation. Additionally, 75% of patients had stone fragments of 4 mm or smaller, and 58% of patients were stone free on CT imaging.

Of the 14 patients with stones in the lower pole, 71% had fragments of 4 mm or smaller and 29% were stone free on imaging. Of the 18 patients with stones in the distal ureter, 89% were completely stone free on imaging.

Regarding safety, no patients experience a serious adverse event (AE), hematoma, cardiac arrhythmia, nor sepsis at any dose level assessed. All patients completed the procedure.

Overall, the open-label, single-arm study enrolled 44 adult patients with renal or ureteral stones across 5 clinical trial sites in the United States and Canada. Patients were enrolled and treated with Break Wave Lithotripsy between August 2019 and February 2022.

Among all patients included in the trial, 73% (32) were male. The median age was 50 years (SD, 14). The average stone size at baseline was 6.1 mm (SD, 1.5; range, 3-9), and the average stone density was 847 HU (SD, 238; range, 450-1346).

To be eligible for enrollment, patients needed to present with at least 1 kidney stone on CT imaging. Additionally, stones needed to be within the upper urinary tract, indicated for shock wave lithotripsy per the American Urological Association (AUA) 2016 guidelines, and had to be measured under CT to be within the AUA 2016 guidelines (≤ 10 mm for lower pole stones and ≤ 20 mm for non-lower pole stones).

Of those included in the trial, 86% received either no medication (50%) or minor analgesia (36%) (e.g., ketorolac 15-30 mg). Patients underwent Break Wave Lithotripsy with the SonoMotion Break Wave technology in either the operating room, the office/clinic, or the emergency department. Patients were followed for 90 days after the procedure.

The primary effectiveness outcome was stone fragmentation, as determined by stone passage or imaging confirmation. The primary safety outcome was the occurrence of clinically significant or symptomatic hematoma, urinary tract sepsis, or cardiac arrhythmia. Secondary effectiveness measures were stone free status and residual fragment size. The secondary safety measure was the occurrence of AEs.

Overall, the authors concluded, “Break Wave Lithotripsy appears to be a safe and effective non-invasive stone therapy requiring little to no anesthesia. It is potentially suitable for non-operative environments such as the office or ED and is being evaluated in ongoing trials.”

1. Chew BH, Harper JD, Sur RL, et al. Break WaveTM lithotripsy for urolithiasis: results of the first-in-human international multicenter clinical trial. Presented at: 2024 World Congress of Endourology and Uro-Technology. Seoul, South Korea. August 12-16, 2024. Abstract MP23-06. https://meetings.association-service.org/docs/wcet/abstracts/abstracts.aspx

2. Break Wave(TM) extracorporeal lithotripter first-in-human study. ClinicalTrials.gov. Last updated April 17, 2024. Accessed August 21, 2024. https://clinicaltrials.gov/study/NCT03811171

Any stone fragmentation was achieved in 88% of patients.

Data suggest Break Wave lithotripsy is safe, effective for urolithiasis

The American Association of Clinical Urologists (AACU) — We would like to invite your participation in the AACU 2024 Advocacy Summit & Annual Meeting. This year we are thrilled to be meeting live, in Washington, DC at the Grand Hyatt, September 22-24.

This year, the AACU 2024 Advocacy Summit & Annual Meeting will focus on the intersection of health policy and clinical practice, as well as the impact of current state and national legislative trends on urology. 

Sunday afternoon we begin with highlighting the integration of new innovative treatments into a urology practice. We will discuss challenges and explore reimbursement solutions. We’ll cover a wide variety of relevant, timely topics, including biomarkers, genetics, step therapy/prior authorization, cancer screenings, BPH and OAB treatments, telehealth, and much more.

The discussion continues through Monday with solution orientated Hot Topics as well as Policy and Advocacy updates on both the state and federal level. For attendees staying through Tuesday, we will provide advocacy training and visits on The Hill. Join us 

The AACU leadership has made it a priority to advocate for access to care for their members’ patients. This can take many forms from meeting with legislators, providing comments to regulators, and working directly with payers. 

AACU ensures that its members’ interests are met through positions on the American Board of Urology and American College of Surgeons as well as delegates to the AMA and representatives on the RUC and CPT Advisory Councils.

This year, the AACU 2024 Advocacy Summit & Annual Meeting will focus on the intersection of health policy and clinical practice, as well as the impact of current state and national legislative trends on urology.

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AACU 2024 Advocacy Summit & Annual Meeting

Treatment Sequencing With Androgen Receptor-Targeted Therapies for mCRPC

When treating with androgen receptor-targeted therapies, what are some of the considerations to make towards the sequencing of these agents and weighing their benefits in first line versus second line?

Key opinion leaders discuss considerations for sequencing androgen receptor-targeted therapies in metastatic castration-resistant prostate cancer, evaluating their benefits in first-line versus second-line treatment settings.

Video Series

Management of Comment Adverse Effects Associated with mCRPC Therapies

How do you manage common side effects associated with mCRPC treatments, including androgen receptor-targeted therapies?

Key opinion leaders explore strategies for managing common side effects associated with metastatic castration-resistant prostate cancer (mCRPC) treatments, including androgen receptor-targeted therapies.

Michael O. Koch, MD

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