Impact of primary resistance to front-line targeted therapy in metastatic renal cell carcinoma on subsequent immune-checkpoint-inhibition

Introduction Synergistic effects have been discussed for tyrosine kinase (TKI) and immune checkpoint inhibitors (ICI). Primary resistance to TKI might disturb subsequent ICI effectiveness. The objective was to investigate, if primary resistance to 1st line TKI monotherapy predicts response to ICI in...

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Published in:Discover. Oncology 2023-09, Vol.14 (1), p.178-178, Article 178
Main Authors: Börner, J. H., Neuberger, S., Juengel, E., Ziewers, S., Dotzauer, R., Sparwasser, P., Höfner, T., Tsaur, I., Haferkamp, A., Mager, R.
Format: Article
Language:English
Subjects:
Anti-VEGF
Cancer Research
Cancer therapies
Consortia
Disease control
Drug dosages
Histology
Immune checkpoint inhibition
Internal Medicine
Kidney cancer
Medical prognosis
Medicine
Medicine & Public Health
Metastasis
Metastatic renal cell carcinoma
Molecular Medicine
Neutrophils
Oncology
Radiotherapy
Remission (Medicine)
Resistance
Sequential therapy
Statistical analysis
Surgical Oncology
Toxicity
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Summary:Introduction Synergistic effects have been discussed for tyrosine kinase (TKI) and immune checkpoint inhibitors (ICI). Primary resistance to TKI might disturb subsequent ICI effectiveness. The objective was to investigate, if primary resistance to 1st line TKI monotherapy predicts response to ICI in subsequent therapy lines and impacts overall survival (OS) in advanced renal cell carcinoma (aRCC). Materials and methods Retrospectively, aRCC patients which received front-line TKI from 2016 to 2019 were analyzed for the outcomes primary resistance (1LR), response to sequential ICI therapy, progression free survival (PFS) and overall survival (OS). Kaplan–Meier-estimates, Cox proportional hazards and logistic regression were used. Results Primary resistance to front-line TKI was observed in 27 (53%) of 51 patients. Groups with disease control (DC) and 1st line TKI resistance (1LR) were not different at baseline with regard to clinicopathological features. Median duration on 1st line therapy was significantly shorter in the 1LR (5.1 months) than in the DC (14.7 months) group (p = 0.01). Sequential therapy was started in 21 (75%) and 12 (52%) patients of 1LR and DC groups using nivolumab in 16 (76%) vs. 11 (92%) cases (p > 0.05). Logistic regression revealed that 1LR status, neutrophil-to-lymphocyte ratio 
ISSN:2730-6011
2730-6011
DOI:10.1007/s12672-023-00791-3