ESTRO 2021 Abstract Book

S492

ESTRO 2021

difference in severe toxicity whether TT/IT was interrupted or not (p=0.373 acute toxicity, p=0.216 for late toxicity). Conclusion This real-life database is the first to prospectively report the risk of toxicity of combined SRT and targeted therapy or immunotherapy in metastatic cancer patients. Overall, severe toxicity was observed in <10% of the patients treated for brain and extracranial metastases. There was no increased toxicity when TT/IT was not interrupted during SRT. OC-0627 A phase II trial of PD-1 inhibitor combined with Radiotherapy and GM-CSF (PRaG) in metastatic tumors L. Zhang 1 , Y. Kong 1 , P. Xing 1 , X. Zhao 1 , G. Chen 2 , Y. Ma 1 , L. Zou 1 , Q. Peng 1 , M. Xu 1 , Z. Xu 3 1 The Second Affiliated Hospital of Soochow University, Department of Radiation Oncology, Suzhou, China; 2 The Second Affiliated Hospital of Soochow University, Department of Radiology, Suzhou, China; 3 Medical Affairs, ICON Plc, Beijing, China Purpose or Objective Programm ed cell death 1 (PD-1) inhibitors have great progress in the treatment of many kinds of metastatic tumors. However, the efficacy of PD-1 inhibitors as monotherapy is still limited due to tumor heterogeneity, high tumor burden, and “cold” tumor microenvironment. Evidences have shown that radiotherapy can induce a systemic antitumor immune resp onse and may have a great potential to sensitiz e PD-1 inhibitors. The add ition of immunomodulatory cytokines such as granulocyte macrophage-colony stimulating factor (GM-CSF) can further improve the synergistic effects. An open-label phase Ⅱ trial was conducted to assess the clinical efficacy and safety of PD-1 inhibitors combined with multisite hypofractionated Radiotherapy (HFRT) and GM- CSF (PRaG regimen) for the treatment of chemo-refractory solid tumor patients. Materials and Methods Subjects with multi-metastatic solid tumors and progressed beyond at least first-line chemotherapy were enrolled. In a PRaG cycle, SBRT or HFRT(3×8Gy or 3×5Gy) was delivered for one metastatic site, GM-CSF 200 µg was subcutaneously injected daily for 2 weeks after radiotherapy, and sintilimab 200mg or toripalimab 240 mg was intravenously administered once within one week after completion of SBRT or HFRT. PRaG was repeated every 21 days for at least 2 cycles. After discontinuation of PRaG and patient had no disease progression, sintilimab or toripalimab monotherapy was given until disease progression or unacceptable toxicity. The primary endpoint is progression-free survival (PFS). This trial is registered in chictr.org.cn (No.ChiCTR 1900020175). Results By February 2021, a total of 48 patients were enrolled. The median number of metastatic lesions was 7 ( 95%CI, 5.0 to 10.0) and the median sum of the longest diameter of all measurable lesions was 122.0mm ( 95%CI, 40.0 to 279.0mm). Forty-three patients ( 89.6%) completed at least two cycles of the triple- combination therapy, and the remaining five patients received one cycle of the triple therapy and continued treatment. Treatment-related adverse events of any grade occurred in 35 (72.9%) patients. The common adverse events were fatigue 52.1%, anorexia 47.9%, thyroid dysfunction 29.2%, liver dysfunction 18.8% and rash 14.6%. Two patients who received radiotherapy for lung lesions developed grade 3 and 4 pneumonia, respectively. Forty-one patients completed at least one efficacy evaluation, seven patients had confirmed partial response (PR), and the objective response rate (ORR) was 14.6% (RECIST 1.1). The median PFS was 5.2 months (95% CI, 4.3-6.1), and the median follow-up time was 9.3 months (95% CI, 6.6-12.0). Conclusion The PRaG regimen is well tolerated with acceptable toxicity . Our data suggest that HFRT and GM-CSF can sensitize the anti-tumor effects of PD-1 inhibitors and result in greater synergistic efficacy. This triple- combination therapy is expected to become a new salvage treatment strategy for patients with chemo- refractory metastatic solid tumors. OC-0628 Regional Control after Stereotactic Radiation therapy and Immunotherapy for NSCLC Brain Metastases J. Porte 1 , C. Saint-Martin 2 , T. Frederic-Moreau 1 , M. Massiani 3 , E. Jadaud 1 , J. Otz 1 , P. Verrelle 4 , N. Girard 5 , G. Créhange 4 , A. Beddok 4 1 Institut Curie, Department of Radiation Oncology, Saint-Cloud, France; 2 Institut Curie, Department of Biostatistics, Paris, France; 3 Institut Curie, Department of Thoracic Oncology, Saint-Cloud, France; 4 Institut Curie, Department of Radiation Oncology, Paris, France; 5 Institut Curie, Department of Thoracic Oncology, Paris, France Purpose or Objective Over the past decade, improvements in the management of advanced non-small-cell lung cancer (NSCLC) through immunotherapy (IT) with PD-1 pathway inhibitors have been significant, with a major improvement in progression-free survival (PFS) and overall survival (OS). Nevertheless, brain metastases (BM) remain frequent at the time of diagnosis (10%) or during the disease (40%). Stereotactic radiation therapy (SRT) has demonstrated its interest in patients with BM from NSCLC, allowing a clear decrease in neurological toxicity compared to that induced by whole brain RT, without loss of OS. The purpose of this study was to analyze locoregional control (LRC), OS, and neurological toxicity in patients with BM from NSCLC treated with IT and SRT and propose the best possible therapeutic sequence between these two treatments. Materials and Methods We retrospectively analyzed NSCLC patients' data with BM treated with IT and SRT within six months between 2015 and 2019. The treated lesions were categorized into the following three groups: “SRT before IT,’’ “concurrent SRT and IT,” and “SRT after IT.’’ “Concurrent” was defined as IT within one month of SRT. Regional progression was defined as the progression or apparition of a BM outside an irradiated area. Regional