Stereotactic radiotherapy combined with immunotherapy or targeted therapy for metastatic renal cell carcinoma

Abstract

Objectives To evaluate the safety and efficacy of stereotactic radiotherapy (SRT) in patients with metastatic renal cell carcinoma (mRCC) concurrently receiving targeted therapy (TT) or immunotherapy. Patients and Methods Data on patients with mRCC were extracted from a retrospective international multicentre register study (TOaSTT), investigating SRT concurrent (≤30 days) with TT/immune checkpoint inhibitor (ICI) therapy. Overall survival (OS), progression‐free survival (PFS), local metastasis control (LC) and time to systemic therapy switch were analysed using Kaplan–Meier curves and log‐rank testing. Clinical and treatment factors influencing survival were analysed using multivariate Cox regression. Acute and late SRT‐induced toxicity were defined according to the Common Terminology Criteria for Adverse Events v.4.03. Results Fifty‐three patients who underwent 128 sessions of SRT were included, of whom 58% presented with oligometastatic disease (OMD). ICIs and TT were received by 32% and 68% of patients, respectively. Twenty patients (37%) paused TT for a median (range) of 14 (2–21) days. ICI therapy was not paused in any patient. A median (range) of 1 (1–5) metastatic tumour was treated per patient, with a median (range) SRT dose of 65 (40–129.4) Gy (biologically effective dose). The OS, LC and PFS rates at 1 year were 71%, 75% and 25%, respectively. The median OS and PFS were not significantly different among patients receiving TT vs those receiving ICIs (P = 0.329). New lesions were treated with a repeat radiotherapy course in 46% of patients. After 1 year, 62% of patients remained on the same systemic therapy as at the time of SRT; this was more frequent for ICI therapy compared to TT (83% vs 36%; P = 0.035). OMD was an independent prognostic factor for OS (P = 0.004, 95% confidence interval [CI] 0.035–0.528) and PFS (P = 0.004; 95% CI 0.165–0.717) in multivariate analysis. Eastern Cooperative Oncology Group performance status (ECOG‐PS) was the other independent prognostic factor for OS (P = 0.001, 95% CI 0.001–0.351). Acute grade 3 toxicity was observed in two patients, and late grade 3 toxicity in one patient. No grade 4 or 5 toxicity was observed. Conclusion Combined treatment with TT or immunotherapy and concurrent SRT was safe, without signals of increased severe toxicity. As we observed no signal of excess toxicity, full‐dose SRT should be considered to achieve optimal metastasis control in patients receiving TT or immunotherapy. Favourable PFS and OS were observed for patients with oligometastatic RCC with a good ECOG‐PS, which should form the basis for prospective testing of this treatment strategy in properly designed clinical trials.

Multidiscipline Immunotherapy-Based Rational Combinations for Robust and Durable Efficacy in Brain Metastases from Renal Cell Carcinoma

“…Data on patients with mRCC were extracted from a retrospective international multicenter registry study, which investigated concurrent stereotactic radiotherapy (SRT) (≤30 days) with ICI therapy [184]. Fifty-three patients who underwent 128 sessions of SRT were included, of which 58% presented with oligometastatic disease [184]. Combined treatment immunotherapy and concurrent SRT were safe, without severe toxicity [184].…”

“…Fifty-three patients who underwent 128 sessions of SRT were included, of which 58% presented with oligometastatic disease [184]. Combined treatment immunotherapy and concurrent SRT were safe, without severe toxicity [184]. Full-dose SRT should be considered to achieve optimal metastasis control in patients receiving immunotherapy [184].…”

“…Combined treatment immunotherapy and concurrent SRT were safe, without severe toxicity [184]. Full-dose SRT should be considered to achieve optimal metastasis control in patients receiving immunotherapy [184]. Favorable PFS and OS were observed in patients with oligometastatic RCC with a good ECOG-PS, which forms the basis for prospective testing of this treatment strategy in properly designed clinical trials [184].…”

Oligometastatic Cancer: Key Concepts and Research Opportunities for 2021 and Beyond

“…Compared with a leukaemia-like dissemination of many malignant processes, the encouraging aspect of a spatially limited oligometastatic disease has ignited a steep rise of scientific interest with new research questions and challenges. We have divided them in three main categories, summarized in Table 1 [ 2 , 3 , 4 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. One of the major drawbacks of the oligometastatic concept is the current perception relying on therapeutic opportunity and cross-sectional imaging rather than intra- and intercellular processes [ 7 ].…”

“…The body of existing evidence, especially from phase III trials, is far from satisfactory, and improvements are already needed at the level of study design with respect to clinical endpoints and the choice of modalities [ 9 , 24 , 29 ]. The latter aspect may indeed be crucial not only due to the large range of possible treatment options and indications, but also because of various combinations and sequencing schedules [ 9 , 14 , 15 , 16 , 17 , 18 ]. It is therefore noteworthy that local ablation should not be used indiscriminately in the oligometastatic setting.…”