Mark D. Tyson, II, MD, MPH, discusses findings from the phase 3 BOND-003 trial in BCG-unresponsive non–muscle-invasive bladder cancer with CIS.

Dr Tyson on the Phase 3 BOND-003 Trial in BCG-Unresponsive NMIBC With CIS

Mark D. Tyson, II, MD, MPH, a urologic oncologist at Mayo Clinic, discusses findings from the phase 3 BOND-003 trial (NCT04452591) in patients with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS).

BOND-003 was an open-label, single-arm study of cretostimogene grenadenorepvec in patients with high-risk BCG-unresponsive NMIBC with CIS. At the April 1, 2024, data cutoff, efficacy-evaluable patients (n = 105) achieved a complete response (CR) rate of 75.2% (95% CI, 65%-83%). Tyson noted that beyond the CR findings, treatment with cretostimogene conferred durable responses; 53.8% of patients who received repeat induction converted to CR. Additionally, 29 patients experienced a duration of response (DOR) of at least 1 year, including 14 patients with a DOR of at least 21 months.

The primary end point of the trial is CR rate at any time. Secondary end points include 12-month CR rate, DOR, progression-free survival, cystectomy-free survival (CFS), and safety.

BOND-003 enrolled a total of 112 patients from North America and the Asia-Pacific region. Eligible patients needed to be at least 18 years old, have pathologically confirmed high-risk NMIBC with carcinoma in situ with or without Ta/T1 disease that is unresponsive to BCG, and have an ECOG performance status of 2 or less.

At baseline, most patients were White (61%), male (74%), and more than 65 years old (83%). The median age was 74 years (range, 43-90) and the median number of previous BCG installations was 12 (range, 7-66).

Regarding safety, no grade or higher 3 treatment-related adverse effects (TRAEs) occurred and there were no deaths. Any-grade TRAEs were reported in 62.5% of patients; the most common TRAEs were bladder spasm (23.2%), pollakiuria (19.6%), dysuria (15.2%), micturition urgency (15.2%), and hematuria (14.2%). Serious adverse effects (AEs) consisted of cystitis (1.8%) and clot retention (1.8%) and 1 patient discontinued treatment due to an AE unrelated to treatment. Nearly all (94.5%) patients completed treatment.

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Mark D. Tyson, MD, urologic oncologist, Mayo Clinic, discusses 2 trials that have shaped physicians’ opinions on the use of neoadjuvant chemotherapy in patients with bladder cancer.

A Medical Research Council trial showed the benefit of 3 cycles of cisplatin, methotrexate, and vinblastine in the neoadjuvant setting for patients receiving radiation, surgery, or radiation plus surgery. That trial showed 6% significance 8 years into the trial.

The SWOG 8710 trial was much more compelling. There was a 31-month survival benefit for patients in the surgical subset who received neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin (MVAC). The patients in the T3 subset experienced a 40-month benefit.

Tyson states that there’s most likely a beneficial effect of neoadjuvant chemotherapy. Whether or not physicians should give gemcitabine and cisplatin or dose-dense MVAC, and the correct number of cycles is still up for debate. Toxicity management still remains a challenge, especially in MVAC.

Mark D. Tyson, MD

Articles

Dr Tyson on the Phase 3 BOND-003 Trial in BCG-Unresponsive NMIBC With CIS

Dr. Tyson on Rationale For Neoadjuvant Chemotherapy in Bladder Cancer