Efficacy and safety of tyrosine kinase inhibitors and low dose immunotherapy in metastatic renal cell carcinoma.

e16518 Background: The Phase-III Checkmate 9ER trial has established cabozantinib and nivolumab as an approved first-line treatment option in patients with metastatic clear-cell renal cell carcinoma (RCC). However, full-dose immunotherapy (IO) imposes significant financial burden in resource-limited settings. We aimed to evaluate the impact of low-dose IO with tyrosine kinase inhibitors (TKI) in our patients. Methods: This retrospective single-center analysis was done at our center from Jan 2019 to Dec 2024. Patients with advanced RCC planned for first-line systemic treatment were included. We assessed treatment efficacy [objective responses (ORR)], safety, pattern of treatment and impact on survival outcomes [progression-free (PFS) and overall survival (OS)] with the addition of low-dose IO (nivolumab 20mg or 40mg) in our patients. Results: Data of 67 patients was analyzed. Median age was 56 years (IQR, 48-63), 85.1% (n=57) were males and 86.6% (n=58) had an ECOG-PS of 0-1. Patients with clear-cell and non-clear cell histology were 64.2% (n=43) and 35.8% (n=24) respectively. Lung is the most common site of metastasis (55.2%, n=37). Among patients with clear-cell histology (IMDC risk details available in n=42/43), 23.8% (n=10/42), 57.1% (n=24/42), and 19.0% (n=8/42) had good, intermediate and poor IMDC risk respectively. First-line treatment with TKI and low-dose IO was given to 72.1% (n=31/43) and 62.5% (n=15/24) patients with a clear-cell and non-clear cell histology respectively, while TKI alone (sunitinib, pazopanib, cabozantinib) was given to 27.9% (n=12/43) and 37.5% (n=9/24) patients respectively. The ORR in patients with a clear- cell histology was 68.0% (n=17/25) with TKI and low-dose IO versus 50.0% (n=5/10) with TKI alone (p=0.319). It was 50.0% (n=6/12) with TKI and low-dose IO versus 0% (n=0/7) with TKI alone (p=0.024) in patients with a non-clear histology. The median follow-up was 11.4 months (95%CI, 8.0-14.8). The median PFS in patients with clear-cell histology was ‘not reached’ with TKI and low-dose IO versus 9.9 months (95%CI, 1.6-18.2, p=0.116) with TKI alone. It was 6.7 months (95%CI, 0.7-12.7) versus 6.5 months (95%CI, 0.0-16.4, p=0.303) in non-clear histology. The median OS was ‘not reached’ in patients with a clear-cell histology, whereas, it was 12.4 months (95%CI, not reached) with TKI and low-dose IO and 14.4 months (95%CI, 8.0-20.8, p=0.890) with TKI alone in the non-clear histology. Conclusions: Limited follow-up showed higher response rates, and a trend towards improved survival with the addition of low-dose nivolumab to TKI in patients with clear-cell RCC. Keyword: Low dose nivolumab, Clear-cell renal cell carcinoma, Tyrosine kinase inhibitors.