ASCO GU 2021: Outcomes of First-Line Immuno-Oncology Combination Therapies in Metastatic Renal Cell Carcinoma: Results from the International mRCC Database Consortium

(UroToday.com) Nivolumab plus ipilimumab and immunotherapy/vascular endothelial growth factor (VEGF) inhibitor combinations are now standard of care first-line treatment options for metastatic renal cell carcinoma (mRCC). However, there is limited head-to-head comparative evidence between these strategies in this evolving treatment landscape in mRCC:

evolving treatment landscape in mRCC

At the 2021 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium, Dr. Chun Gan and colleagues presented results of outcomes of first-line immuno-oncology combination therapies in mRCC from the International Metastatic RCC Database Consortium (IMDC) database.

In this study of the IMDC dataset, patients treated with first-line immunotherapy/VEGF inhibitor combinations (pembrolizumab plus axitinib, avelumab plus axitinib, and nivolumab plus cabozantinib) were compared with those treated with nivolumab plus ipilimumab. The outcomes of interest were overall response rate, treatment duration, time to next treatment, and overall survival. A preplanned subgroup analysis of the IMDC intermediate/poor risk population was conducted, and hazard ratios were adjusted for IMDC risk factors.

There were 723 patients included for analysis, including 571 patients receiving nivolumab plus ipilimumab and 152 patients receiving immunotherapy/VEGF inhibitor combinations. The proportion of patients with IMDC favorable, intermediate and poor-risk disease in nivolumab plus ipilimumab versus immunotherapy/VEGF inhibitor combination groups were 9% versus 33%, 58% versus 53%, 33% versus 14%, respectively. In the intermediate/poor risk groups, objective response rate (37% versus 59%) and median treatment duration (4.6 versus 15.0 months) were lower and shorter in nivolumab plus ipilimumab versus immunotherapy/VEGF inhibitor combinations:

treatment duration in nivolumab plus ipilimumab versus immunotherapyVEGF inhibitor combinations

However, there was no difference in median time to next therapy and overall survival detected between these groups:

overall survival in nivolumab plus ipilimumab versus immunotherapyVEGF inhibitor combinations

The hazard ratio for death adjusting for IMDC criteria for nivolumab plus ipilimumab versus immunotherapy/VEGF inhibitor combinations was 0.92 (95% confidence interval [CI] 0.61-1.40, p=0.71). IMDC risk groups and the presence or absence of sarcomatoid histology, brain, liver, or bone metastases were not associated with differences in overall survival between these treatments (all p>0.2). Patients that had dose delays or steroid use (defined as >40mg of prednisone equivalent/day) for immune-related adverse events were associated with a longer median time to next treatment (21.6 vs. 9.5 months, p=0.02) and overall survival (not reported [NR] vs. 44.4 months, p=0.01) despite similar treatment durations (7.6 vs. 8.9 months, p=0.77) compared to those without dose delays or steroid use.

Dr. Gan provided the following summary statements for this presentation:

  • While there were a longer treatment duration and higher objective response rate with immunotherapy/VEGF inhibitor combinations, there were no differences in overall survival and time to next treatment detected between nivolumab plus ipilimumab and immunotherapy/VEGF inhibitor combinations in the IMDC intermediate/poor-risk patients
  • Serious immune-related adverse events were associated with improved overall survival and time to next treatment
  • Both nivolumab plus ipilimumab and immunotherapy/VEGF inhibitor combinations are reasonable first-line strategies
Presented by: Chun L. Gan, MD, Fellow of Urologic Oncology, Tom Baker Cancer Center, University of Calgary, Calgary, Alberta, Canada

Written by: Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Augusta, Georgia, Twitter: @zklaassen_md during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021
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