Nivo, Chemoradiotherapy for Patients With nmMIBC Not Undergoing Cystectomy

The addition of nivolumab to trimodality therapy may improve relapse-free survival in patients with non-metastatic muscle-invasive bladder cancer (nmMIBC), according to results of a phase 2 randomized study by the Hellenic GU Cancer Group.

Results are presented at the European Society for Medical Oncology Congress 2024.

For patients with nmMIBC who cannot undergo or refuse radical cystectomy, trimodality therapy with maximal effort transurethral resection of bladder tumor (TURB-T) plus chemoradiotherapy (CRT) is considered an effective treatment alternative.

Dr. Andromachi Kougioumtzopoulou and colleagues at the Hellenic GU Cancer Group designed a study to investigate the effect of concurrent nivolumab in addition to CRT in 72 patients with nmMIBC who did not undergo radical cystectomy from June 2019 to October 2022.

Eligible patients included those with stage cT2–T4a N0 M0 disease who previously underwent optimal TURB-T. Patients were randomized to receive nivolumab (240 mg every 2 weeks) concurrently to CRT (14 days prior to radiotherapy initiation) followed by 6 cycles of nivolumab (480mg every 4 weeks; n=37) or to CRT (cisplatin concurrently with radical radiotherapy) alone (n=35).

Dose escalation radiotherapy to 66-70 Gy (2 Gy per fraction) was administered in both treatment arms, the researchers noted. The primary endpoint of the study was 2-year locoregional or distant relapse-free survival.

After a follow-up of 17.7 months, nine patients relapsed in the nivolumab-plus-CRT arm and 16 patients relapsed in the CRT-alone arm. Two-year relapse-free survival was 59.9% and 37.6%, respectively (P=.04). In addition, Dr. Kougioumtzopoulou and colleagues found that the median overall survival was not reached at 24 months, respectively.

Anemia and thyroid dysfunction were the most frequently observed adverse events in the nivolumab-plus-CRT arm. Grade 3 or higher adverse events were reported in 24 patients: 14 in the nivolumab-plus-CRT arm and 10 in the CRT-alone arm. No treatment-related deaths occurred.

“The addition of nivolumab to trimodality therapy produced a significant increase in relapse-free survival without any new safety signals being observed,” Dr. Kougioumtzopoulou and colleagues concluded. “These results warrant the conduction of a randomized phase 3 trial to establish nivolumab plus CRT as a new standard for patients with nmMIBC not undergoing radical cystectomy.”