Preliminary results from a phase II clinical study of first-line drugs combined with stereotactic body radiotherapy (SBRT) in the treatment of oligoprogressive renal cell carcinoma.

4540 Background: For metastatic renal cell carcinoma (mRCC) patients (pts) with oligoprogression, escalation of systemic therapy (STE) to the next line of treatment is one of the major strategies but not the only option. Our study aimed to investigate the safety and efficacy of stereotactic body radiotherapy (SBRT) to mRCC pts with oligoprogression after first-line systemic therapy. Methods: This is a single-arm, phase II study enrolling oligoprogressive mRCC pts, defined as ≤ 3 progressive lesions with total metastases ≤ 5, who have received first-line systemic therapy for more than three months (ChiCTR2000032947). No liver or brain metastasis was allowed. Nephrotic focus was treated before or after enrollment. Pts remained on current first-line systemic therapy and received SBRT for all the oligoprogressive lesions, with 35-45Gy in 5 fractions. If oligoprogressive lesions appeared > 6 months after the end of SBRT, which were not irradiated, a second round of SBRT could be allowed. Primary endpoint was progression-free survival (PFS); secondary endpoints were local control (LC) rate, time to STE, overall survival (OS) and safety. Results: From June 2020 to Jan 2024, 30 pts were enrolled, and 27 pts (median age: 55 years; male-to-female ratio: 16:11) were evaluable for efficacy after SBRT. Most pts (74.1%) had a clear cell histology, and most pts (92.6%) were at an intermediate or a poor risk according to the International Metastatic RCC Database Consortium criteria. Sixteen pts had one progressive lesion and 11 pts had 2-3 lesions. The median time to oligoprogressive disease under first-line systemic therapy (mostly TKI monotherapy: 85.2%) was 13.6 months. The most common sites for SBRT were bone (32.4%), lymph node (23.5%) and lung (23.5%). At a median follow-up of 23.5 months, the LC rate was 97.1%. Six-month PFS, 12-month PFS, 18-month PFS, 24-month PFS and median PFS were 88.9%, 54.2%, 36.4%, 22.7% and 15.0 months, respectively. The 24-month OS and median OS were 78.5% and not reached. Grade 3-4 treatment-related adverse events (AEs) occurred in 44.4% pts, and the most common AEs were hematological toxicity (18.5%), hypertension (18.5%), and palmar-plantar erythrodysesthesia syndrome (7.4%). No SBRT-related grade 3-4 toxicity was observed. Conclusions: SBRT is a safe and an effective treatment for oligoprogressive mRCC, with a notable extension of the ongoing first-line systemic therapy. Clinical trial information: ChiCTR2000032947.