Real-world survival outcomes associated with immunotherapy followed with anti-vascular targeted therapy for metastatic clear cell renal cell carcinoma.

e16507 Background: The Food and Drug Administration (FDA) has approved a variety of drugs for the treatment of advanced metastatic renal cell carcinoma, including anti-vascular tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). Options for initial therapy range from monotherapy to combination therapy. However, the challenge of choosing the most effective first- and second-line treatments to enhance overall survival persists. Methods: In this retrospective, propensity-matched cohort study, we included 135 patients with metastatic clear cell renal cell carcinoma (mRCC) treated at Shandong Cancer Hospital between January 1, 2017, and December 31, 2022. These patients received ICIs as part of their first or second line of therapy. Statistical analysis was conducted from June 1, 2023, to August 1, 2023. The primary endpoint was OS, measured from the date of diagnosis to death or the last follow-up. PFS was assessed during treatment. Survival analysis was performed using Cox proportional hazards regression and Kaplan-Meier estimates. Results: The final cohort comprised 135 patients, of whom 84 received first-line therapy with ICIs. The remaining 51 patients were treated with ICIs as second-line therapy following an initial regime of TKIs. Patients were initially categorized based on whether ICIs were used in the first-line treatment. It was observed that the OS for patients receiving first-line targeted therapy was higher than for those receiving first-line immunotherapy, with median OS figures of 33 months versus 15 months. To investigate this outcome, we further refined the patient groups based on the sequence of ICIs and TKIs in the treatment regimen. We discovered that the median PFS following first-line anti-vascular targeted therapy combined with immunotherapy was 3.5 months, compared to 14.5 months when immunotherapy followed first-line anti-vascular targeted therapy (p=0.0092). The median PFS for second-line treatments was 6.5 months versus 15 months (p=0.0014). Similarly, the median OS figures were 16.66 months and 31.88 months, respectively (p=0.008). Conclusions: This study suggests that administering immunotherapy after the progression of anti-vascular therapy significantly improves both OS and PFS compared to other sequences of immunotherapy. These findings offer valuable insights and strong empirical support for clinical decision-making regarding the sequencing of treatments for mRCC.