Distinct pathways of disease progression with dual checkpoint blockade versus immunotargeted therapy in metastatic renal cell carcinoma

Tsimafeyeu I. Guliyev F. Ongarbayev B. Musaeva G. Abdrakhmanov R. Chubenko V. Baklanova O. Zukov R. Petkau V. Kaidarova D.
April 2026 Elsevier Inc.

Urologic Oncology: Seminars and Original Investigations
2026 #44 Issue 4

Background Patterns of progression under immuno-oncology regimens in metastatic renal cell carcinoma (mRCC) remain poorly described. This study characterizes site-specific disease progression in patients receiving first-line dual immunotherapy or immunotargeted therapy. Methods This retrospective, observational cohort study included patients with clear-cell metastatic renal cell carcinoma treated between 2018 and 2024 with standard-dose regimens of nivolumab-ipilimumab (IO-IO) or pembrolizumab-axitinib and avelumab-axitinib combinations (IO-axitinib). The primary endpoint was the occurrence of new metastatic lesions at progression. Secondary endpoints included progression by 20% increase in target lesion size. Results Of 334 patients identified, 233 were evaluable for analysis. Radiographic progression occurred in 86.3% of IO-IO and 60% of IO-axitinib. Development of new metastatic lesions was more frequent with Nivo-Ipi (39.3% vs. 22.2%), most commonly involving the lungs and bones. In contrast, IO-axitinib combinations showed a greater propensity for progression through enlargement of pre-existing lesions (77.8% vs. 60.7%), accompanied by the emergence of new adrenal gland metastases. Across both treatment groups, lymph nodes emerged as the most frequent new site of disease progression. Conclusions Nivo-Ipi was associated with more frequent development of new metastatic lesions, particularly in the lungs, bones, and lymph nodes, while axitinib-based combinations more often resulted in regrowth of existing disease with higher rates of adrenal involvement.

Immunotherapy combinations , Metastatic renal cell carcinoma , Organ-specific metastases , Progression patterns

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Bureau for Cancer Research - BUCARE, NY, United States
National Center of Oncology, Baku, Azerbaijan
Kazakh Institute of Oncology and Radiology, Almaty, Kazakhstan
Saint-Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care Oncological, Saint-Petersburg, Russian Federation
Irkutsk Regional Cancer Center, Department of Urology, Irkutsk, Russian Federation
V.F. Voyno-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation
Sverdlovskiy Regional Oncological Dispensary, Ekaterinburg, Russian Federation
Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan

Bureau for Cancer Research - BUCARE
National Center of Oncology
Kazakh Institute of Oncology and Radiology
Saint-Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care Oncological
Irkutsk Regional Cancer Center
V.F. Voyno-Yasenetsky Krasnoyarsk State Medical University
Sverdlovskiy Regional Oncological Dispensary
Asfendiyarov Kazakh National Medical University

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Книга Публикация научной статьи Волощук 2026 Book Publication of a scientific article 2026