ASCO GU 2025: Real-World Outcomes of First-Line Dual Immunotherapy Versus Combination VEGF Immunotherapy in Intermediate-Poor Risk Metastatic Renal Cell Carcinoma: Results from the International Metastatic Renal Cell Carcinoma Data Consortium (IMDC)

(UroToday.com) The 2025 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Annual Symposium held in San Francisco, CA between February 13–15, 2025 was host to a renal cell, adrenal, penile, testicular, and urethral cancers poster session. Dr. David Maj presented an analysis of the International Metastatic Renal Cell Carcinoma Data Consortium (IMDC) evaluating real-world outcomes of first-line dual immunotherapy versus combination VEGF immunotherapy in intermediate-poor risk metastatic renal cell carcinoma (mRCC).


Current first-line therapy for mRCC is dual immunotherapy (IPI-NIVO) or a combination of immunotherapy with a VEGFR inhibitor (IOVE). Data from CheckMate-214 suggests that there may be durable disease control with Ipi-Nivo that has not been seen in IOVE trials.1 Real world data is lacking to compare the relative effectiveness of these regimens 

Using the IMDC, Dr. Maj and colleagues performed a retrospective analysis of patients with intermediate or poor risk disease (≥1 IMDC risk factor), who received first-line therapy with

IPI-NIVO or an approved IOVE combination (avelumab + axitinib, nivolumab + cabozantinib, pembrolizumab + axitinib, or pembrolizumab + lenvatinib). The baseline characteristics, objective response rates (ORR), time to next therapy (TTNT), and overall survival (OS) were compared between IPI-NIVO and IOVE regimens using Cox regression analyses.

The baseline patient characteristics are summarized below. Compared to patients in the IPI-NIVO group, those in the IOVE group were more likely to be older than 65 years old (32% versus 26%, p=0.02) and have bone metastases (43% versus 34.3%, p=0.003). Baseline characteristics were otherwise well-balanced.The baseline patient characteristics are summarized below. Compared to patients in the IPI-NIVO group, those in the IOVE group were more likely to be older than 65 years old (32% versus 26%, p=0.02) and have bone metastases (43% versus 34.3%, p=0.003). Baseline characteristics were otherwise well-balanced.
The ORR was superior in the IOVE group (48% versus 39%, p=0.004). This was mainly driven by higher partial response rates (45.6% versus 32.2%).
The ORR was superior in the IOVE group (48% versus 39%, p=0.004). This was mainly driven by higher partial response rates (45.6% versus 32.2%).
With regards to OS, on multivariable analysis adjusted for IMDC criteria, presence/absence of brain, bone, and liver metastasis, there were no significant differences in survival rates (HR: 0.87, 95% CI: 0.71–1.06, p=0.17).
With regards to OS, on multivariable analysis adjusted for IMDC criteria, presence/absence of brain, bone, and liver metastasis, there were no significant differences in survival rates (HR: 0.87, 95% CI: 0.71–1.06, p=0.17).
Differences in survival remained non-significant in an exploratory analysis limited to patients with clear cell histology, ECOG 0-2, and no brain metastasis (p=0.73). 

There were no subgroup differences in OS, when stratified by presence/absence of bone metastasis (p=0.98), liver metastasis (p=0.16), lung metastasis (p=0.34), or performance status (p=0.79).

The median time to next treatment in IMDC intermediate-poor risk patients was longer in the IOVE-treated patients (median: 18.6 versus 10.4 months; HR: 0.71, 95% CI: 0.60–0.83, p<0.0001).
The median time to next treatment in IMDC intermediate-poor risk patients was longer in the IOVE-treated patients (median: 18.6 versus 10.4 months; HR: 0.71, 95% CI: 0.60–0.83, p<0.0001).
Patients receiving IPI-NIVO were more likely to discontinue therapy (75% vs 62%, p<0.0001). There were no significant differences in immune-related adverse events (p=0.09) or reason for immunotherapy discontinuation (p=0.23). 

Based on this data, Dr. Maj concluded that first-line ipilimumab + nivolumab and immunotherapy + VEGF regimens have similar real-world survival outcomes.

Presented by: David Maj, MBBS, MSc, Department of Oncology, Arthur JE Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB, Canada

Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025. 

Reference:
  1. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med 2018; 378(14):1277-90.