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AUA 2025

AUA 2025: Primary Resistance to Nivolumab plus Ipilimumab Therapy Affects Second-Line Treatment Outcomes in Patients with mRCC

(UroToday.com) The American Urologic Association (AUA) 2025 Annual Meeting, held in Las Vegas, NV, between April 26th and 29th, 2025, was host to an advanced kidney cancer moderated poster session. Dr. Kazuyuki Numakura presented a study of primary resistance to nivolumab + ipilimumab therapy affecting second-line treatment outcomes in metastatic renal cell carcinoma (mRCC) patients.

Long-term follow-up from the phase III CheckMate 214 trial demonstrated that nivolumab + ipilimumab, compared to sunitinib monotherapy, is associated with superior overall survival (median: 53 versus 37 months) and objective response rates (39% versus 32%), including complete responses (12% versus 3%).1 However, up to 20% of patients receiving nivolumab + ipilimumab in the 1st line setting are not expected to derive a response from systemic therapy and have poor outcomes. 

Dr. Numakura and colleagues analyzed 189 patients from the JUOG database who received first-line nivolumab + ipilimumab systemic therapy. Of the 189 patients, 42 patients demonstrated progressive disease within three months of initiating first-line nivolumab + ipilimumab, defined as “primary resistance disease” (PRD). In the 2nd line setting, 18 cases were treated with cabozantinib, 17 with axitinib, and 7 with other drugs.

Dr. Numakura and colleagues analyzed 189 patients from the JUOG database who received first-line nivolumab + ipilimumab systemic therapy. Of the 189 patients, 42 patients demonstrated progressive disease within three months of initiating first-line nivolumab + ipilimumab, defined as “primary resistance disease” (PRD). In the 2nd line setting, 18 cases were treated with cabozantinib, 17 with axitinib, and 7 with other drugs.
Patients without primary resistance disease (i.e., non-PRD) had significantly superior progression-free, time to second progression-free, and overall survivals, compared to the PRD group, with median survivals of 9, 20, and >48 months, respectively. No significant survival differences were observed by the drug therapy received in the 2nd line setting.

Dr. Numakura noted that the IMDC risk at the start of second-line treatment was significantly worse in the PRD group, and the performance status before initiating second-line treatment was poor in the PRD group.
Dr. Numakura noted that the IMDC risk at the start of second-line treatment was significantly worse in the PRD group, and the performance status before initiating second-line treatment was poor in the PRD group. 

Dr. Numakura concluded as follows:

  • Patients with primary resistance disease to nivolumab + ipilimumab also had poor survival outcomes with second-line treatments
  • A high proportion of these patients had IMDC poor risk and poor performance status before second-line treatment, which may have influenced the efficacy of VEGFR-TKI in second-line therapy.
  • The type of VEGFR-TKI used in second-line treatment did not affect the therapeutic outcome.

Presented by: Kazuyuki Numakura, MD, Department of Urology, Akita University Graduate School of Medicine, Akita, Japan

Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the 2025 American Urological Association (AUA) annual meeting held in Las Vegas, NV, Saturday, April 26 - Tuesday, April 29, 2025

References:
  1. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus ipilimumab (NIVO+IPI) vs sunitinib (SUN) for first-line treatment of advanced renal cell carcinoma (aRCC): Long-term follow-up data from the phase 3 CheckMate 214 trial. J Clin Oncol 2023; 41(6_suppl): 291.