Top 10 Genitourinary Cancer Advances in 2024

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New FDA approvals, pivotal clinical trial results, and innovative treatment strategies emerged in the field of genitourinary cancers in 2024. Here are 10 of the top developments from the field this year:

FDA Approval of Nivolumab Combination for Urothelial Carcinoma:

In March 2024, the FDA approved nivolumab (Opdivo) in combination with cisplatin and gemcitabine as a first-line treatment for adults with unresectable or metastatic urothelial carcinoma. Data from the phase 3 CheckMate-901 study (NCT03036098) supported the approval as the addition of nivolumab to chemotherapy led to higher objective response rates (ORR), including a greater proportion of complete responses, and a longer median duration of response vs chemotherapy alone.

Erdafitinib Approval for FGFR3-Altered Urothelial Carcinoma:

In January 2024, the FDA approved erdafitinib (Balversa) for adult patients with locally advanced or metastatic urothelial carcinoma harboring susceptible FGFR3 genetic alterations, following progression on prior systemic therapy, as supported by data from the THOR study (NCT03390504).

Positive Phase 3 Results for Durvalumab in Muscle-Invasive Bladder Cancer

In the phase 3 NIAGARA trial (NCT03732677), the combination of neoadjuvant durvalumab (Imfinzi) plus chemotherapy, followed by adjuvant durvalumab, led to significantly improved rates of event-free survival and overall survival (OS) in patients with cisplatin-eligible muscle-invasive bladder cancer, vs neoadjuvant chemotherapy plus placebo. These benefits observed in the study were reached without affecting patients' ability to undergo radical cystectomy.

Breakthrough Immunotherapy for Bladder Cancer:

An experimental immunotherapy, cretostimogenegrenadenorepvec showed promise in the phase 3 BOND-003 trial (NCT04452591) with 112 patients with high-risk Bacillus Calmette-Guérin-unresponsive non–-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ. Sustained and durable CRs over 12 months with a CR rate of 75.2% were seen, according to an interview between Targeted Oncology^TM and Mark D. Tyson, II, MD, MPH, a urologic oncologist at Mayo Clinic in Phoenix, Arizona.

Belzutifan Improves Survival vs Everolimus in Advanced RCC:

Belzutifan (Welireg) showed a significant benefit in progression-free survival (PFS) and ORR when compared with everolimus among patients with advanced clear cell renal cell carcinoma (RCC) previously treated with immune checkpoint and antiangiogenic therapies, according to the results of the phase 3 LITESPARK-005 study (NCT04195750).

FDA Biologics License Application Submission of TLX250-CDx for RCC:

The biologics license application (BLA) submission of TLX250-CDx (Zircaix, 89Zr-DFO-girentuximab) for the FDA was completed in June 2024. TLX250-CDx, an investigational radiodiagnostic PET being developed for the characterization of renal masses as clear cell RCC, was studied in the phase 3 ZIRCON study (NCT03849118), and data from this trial support the BLA.

Nadofaragene Firadenovec Fully Available Across US for BCG-Unresponsive NMIBC: 

Nadofaragenefiradenovec-vncg (Adstiladrin) is the first FDA-approved intravesical gene therapy for adults with NMIBC who are no longer responsive to standard treatments. This therapy is now available nationwide, with healthcare providers able to prescribe it for patients with NMIBC and carcinoma in situ, with or without papillary tumors, while the ABLE-41 U.S. study (NCT06026332) continues to evaluate its effectiveness.

Real-World Study Shows ICI Therapy Effectiveness in Black Patients With RCC

A real-world study conducted by researchers at Fox Chase Cancer Center suggests that treatment recommendations for Black and White patients with metastatic RCC should be the same, with immune checkpoint inhibitor–-based therapy (ICI) offered to both groups. The study found that ICI was equally effective as a frontline treatment for both Black and White patients, with both groups experiencing improved real-world PFS vs those treated with sunitinib (Sutent).

TPST-1120 With Nivolumab Shows Promise in RCC

TPST-1120, a first-in-class oral inhibitor of PPAR-α, was found to be well tolerated both as monotherapy and in combination with nivolumab (Opdivo) in patients with PD-1 inhibitor–-refractory cancers, including RCC. In the combination arm, 20% of patients showed an ORR, with 30% response in those receiving 400 mg or higher of TPST-1120 twice daily, while 53% of patients in the monotherapy arm achieved stable disease.

Pembrolizumab/Cabozantinib Shows Encouraging Preliminary Efficacy in mRCC

The combination of pembrolizumab (Keytruda) and cabozantinib (Cabometyx) showed promising preliminary efficacy and a manageable toxicity profile in patients with metastatic RCC, as demonstrated in a phase 1/2 trial (NCT03149822). Among the 38 evaluable patients, the ORR was 65.8%, with a median PFS of 10.45 months and a median OS of 30.81 months at a median follow-up of 23.5 months.

Each of these developments offers new avenues for treatment and improved patient outcomes for patients with genitourinary cancers.