3184 - A Phase Il Clinical Study of Axitinib and Toripalimab Combined with Stereotactic Radiation (SBRT) for Metastatic Renal Cell Carcinoma (mRCC) after Oligoprogression from First-Line Anti-Angiogenic Ther

R. Liu¹, Y. Liu¹, X. Zhang², W. Wei², J. Gao², Z. Zhang², S. Guo², H. Han², F. Zhou², P. Dong², L. He¹, and L. Cai¹; ¹State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China, ²Sun Yat-sen University Cancer Center, Guangzhou, China

Purpose/Objective(s): The objective of this study was to investigate the safety and efficacy of axitinib and toripalimab combined with SBRT as second-line therapy in mRCC who presented with oligoprogression during first-line treatment. Materials/

Methods: In this single-arm, single-center phase ll study, mRCC patients (pts) with oligoprogression (number of progression lesions=3) after first-line anti-angiogenic therapies were enrolled. Pts had at least one measurable lesions=6cm (According to RECIST 1.1 or MDA criteria for bone metastases). Eligible pts received toripalimab (240 mg every 3 weeks) and axitinib (5 mg twice daily) until PD or unacceptable toxicity. Dose of SBRT and number of fractions were determined based on the target lesion localization, size and the proximity of organs at risk individually. The primary endpoint was the progression free survival (PFS), The secondary endpoints included objective response rate (ORR), overall survival (OS), 1-year local control rate and quality of life (QOL) and safety profile.
Results: Sixteen pts were enrolled from June 2018 to January 2024. Median age was 53.5 years. Ten (62.50%) pts were male, while 11 (68.8%) pts were clear cell renal cell carcinoma. Seven (43.75%) pts had multiple metastases (n>5), while 10 (62.50%) pts were IMDC intermediate (9) or high (1) risk. The median duration of prior first-line therapy was 9.98 months (range 1.93 to 59.10 months). Of the 16 pts, 10 (62.50%) had bone metastases, 9 (56.25%) had lung metastases, 8 (50.55%) had lymph node metastases, 3 (18.75%) had liver metastases and 1 (6.25%) brain metastasis. There were 1, 4, 4 and 7 pts received SBRT to 4, 3, 2 and 1 oligometastatic lesions, respectively. Three pts received a secondary-round SBRT due to oligoprogression after enrollment. A total of 31 lesions underwent SBRT, of which 10 were bone metastases, 6 were lung metastases, 6 were lymph node metastases, 4 were liver metastases, 3 were soft tissue metastases, 1 was adrenal and 1 was brain metastasis. The most commonly prescribed dose of SBRT is 40Gy/5f (range 30-50Gy/3-7f). After the treatment, the best ORR was 43.75% (CR=2, PR=5, SD=7, PD=2). ORR for the irradiated lesions was 96.77% (CR=15, PR=15 and SD=1). At a median follow-up of 26 mo (range 8.87-43.97 mo), mPFS was 21.87mo and mOS was not reached, 2-year PFS and 2-year OS rate were 39.8% and 78.3%, respectively. 3 grade or higher AEs occurred in 7 pts, including immune pneumonitis (25%,4/16), immune myocarditis (6.3%,1/16), immune hepatitis (6.3%,1/16), hydropericardium (6.3%,1/16).
Conclusion: Axitinib and toripalimab combined with SBRT is effective as second-line therapy with acceptable side effects for mRCC pts who presented with oligoprogression during first-line anti-angiogenic treatment.