Efficacy and safety of SABR with TKI and IO therapy in patients with mRCC.

Abstract

529 Background: Metastatic RCC is a deadly disease and TKI in combination with IO has become a standard therapy for most patients. But some of the pts may present with oligo-metastasis and some with meta site related symptoms. SABR (Stereotactic Ablative Body Radiotherapy) has been proved to be highly effective for RCC in some studies and with potential immune-enhancing ability. The purpose is to investigate the efficacy and safety of SABR with TKI and IO therapy in pts with mRCC. Methods: This is an ambispective cohort study including pts receiving SABR with TKI and IO at the same time. The primary endpoint was PFS. Secondary endpoints included OS, ORR, DCR and TTTC (Time to treatment change). We also analyzed some of the pts’ gene characteristics to investigate the relationship between gene alterations and prognosis. Adverse events were evaluated according to CTCAE 5.0. Results: Until Aug 2024, we retrospectively analyzed pts from Mar 2020 to Mar 2024, and prospectively from Mar 2024 to May 2024. A total of 79 pts were included, of whom 72.2% were with ccRCC, 68.4% were with oligo-metastases (≤5 meta sites), and 83.5% were combined with SABR before 1st-line systemic therapy failure. All pts were categorized to IMDC intermediate or poor prognosis group and TKI and IO combination was used in all pts. All pts with oligo-metastases received SABR for all tumor sites and others were for cytoreductive purpose.The median follow-up was 20.3 mo. The mPFS was 28.6 mo and TTTC was 31.8 mo. The ORR was 68.4% and the DCR was 89.9%. The DCR of radiation lesions was 96.2%. The mOS was 44.8 mo. For pts received SABR before or after 1 st -line systemic therapy failure, the mPFS were 30.6 mo vs. 9.6 mo, respectively (p=0.004). In addition, The NGS analysis was performed in 25 pts tumor samples. The most frequent genes mutated were VHL (60%), SETD2 (24%), ARID1A (24%), TP53 (20%), PTEN (20%), TEF3 (16%), BAP1 (12%), RET (12%), and PBRM1 (12%). We discovered a favorable trend in the prognosis for PFS in pts with tumors purely driven by VHL loss. Mutations in the mTOR pathway genes, PTEN and HRR-related genes appeared to lead to poorer PFS. However, due to limited sample size, statistical significance was not reached. Grade 3 or above AE was 50.2%, and there was no treatment-related death. Conclusions: Targeted therapy combined with immunotherapy and stereotactic radiotherapy has achieved satisfactory survival results for mRCC, and early intervention by SABR may lead to a better PFS. Clinical trial information: ChiCTR2200059204 .