ESTRO 2020 Abstract book

S688 ESTRO 2020

PO-1217 Safety of Nivolumab and stereotactic RT in metastatic renal carcinoma: early results of NIVES study P. Ciammella 1 , G. Timon 1 , C. Masini 2 , R.S. Belli 3 , F. Salaroli 4 , R. Mazzarotto 5 , A. Bruni 6 , C. Pinto 2 , C. Iotti 1 1 AUSL di Reggio Emilia - IRCCS, Radiation Oncology, Reggio Emilia, Italy ; 2 AUSL di Reggio Emilia - IRCCS, Medical Oncology, Reggio Emilia, Italy ; 3 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Radiation oncology, Meldola, Italy ; 4 Azienda Ospedaliero - Universitaria di Parma, Radiation Oncology, Parma, Italy ; 5 Azienda ospedaliera universitaria Integrata di Verona, Radiation Oncology, Verona, Italy ; 6 Azienda Ospedaliero - Universitaria di Modena, Radiation Oncology, Modena, Italy Purpose or Objective Nivolumab (NIVO) is an anti-programmed cell death-1 ligand 1 (PDL-1) monoclonal antibody, which has drastically changed the treatment of metastatic renal cell carcinoma (mRCC). The drug might work even better when combined with radiation therapy, particularly with stereotactic body radiotherapy (SBRT). Tumor PD-L1 expression can suppress the anti-tumor immune response, so inhibition of PD-1/PD-L1 axis has been shown to improve anti-tumor immunity by blocking the tumor-mediated suppression of cytotoxic T cells. Radiation-induced cell death can enhance antitumor immunity by inducing antigen expression on tumor cells and activating lymphocytes. Combining SBRT with nivolumab may enhance the antitumor immune responses and improve clinical outcomes. To date there are limited data on safety profile of combined SBRT and NIVO in mRCC, and hereby we report early results in terms of toxicity. Material and Methods This is a phase II, single arm, multicentre study for patients (pts) with mRCC with progression disease after ≤2 prior anti-angiogenic therapies and with measurable non-brain metastatic sites, at least one of which potentially suitable for SBRT. Patients received the first infusion of NIVO, followed by SBRT to one lesion to a total dose of 30 Gy in 3 fractions after 7 days. NIVO was then administered as flat dose of 240 mg every 14 days for 6 months, then switch to 480 mg q4-weekly in responding patients until progression or unacceptable toxicity. The primary endpoint of this study was to assess the objective response rate (ORR), defined as the best response recorded on the ITT population according to RECIST v1.1. Our hypothesis was that treatment with NIVO + SBRT could improve the ORR from 25% to 40% compared to NIVO alone. Secondary endpoints were PFS, OS, ORR of irradiated and non-irradiated metastases, duration of response and safety profile. In this early report of NIVES Study, descriptive statistics are reported for observed Adverse Events (AEs) according to Common Terminology Criteria for Adverse Events (CTCAE) v. 4.03. Results Sixty-nine patients were enrolled from July 2017 to March 2019 in 12 Italian centers. The enrollment of the study is completed. Figure 1 shows irradiated sites. At the time of this analysis toxicities of grade (G) 3-4 related to NIVO were experienced in 17 pts (24,6%); all G3- 4 toxicities were outside of the irradiated area. To date no G3-4 pneumonitis were observed. Six pts (8.7%) were hospitalized due to treatment-related SAEs. Overall, 5 of 69 treated pts (7.2%) discontinued therapy because of G3- 4 AEs. The addition of SBRT to the treatment didn’t lead to an increase of therapy’s interruptions or delays compared to Nivolumab alone. AEs are reported in Table 1.

PO-1216 Can sarcopenia predict outcomes in bladder cancer patients treated with chemoradiotherapy? M. Corden 1 , S. Chin 2 , A. Cree 2 , P. Hoskin 1 , A. McWilliam 1 , A.D. Satiti 1 , Y.P. Song 2 , A. Green 1 , A. Choudhury 1 1 The University of Manchester, Radiotherapy Related Research, Manchester, United Kingdom ; 2 The Christie NHS Foundation Trust, Clinical Oncology, Manchester, United Kingdom Purpose or Objective Bladder cancer is the tenth commonest malignancy in the UK, with approximately 10,200 new diagnoses and 5,400 deaths annually. Sarcopenia shows promise as a prognostic factor for bladder cancer and has been shown to predict overall survival (OS) in patients treated with radical cystectomy. The present study aims to assess sarcopenia as a predictor of OS and progression-free survival (PFS) in patients with urothelial carcinoma (UC) of the bladder treated with organ-sparing concurrent gemcitabine and 244 patients with non-metastatic UC, treated from 2010- 2017 with 52.5Gy in 20 fractions of curative intent radiotherapy with weekly gemcitabine, were identified for analysis. Pre-treatment computed tomography (CT) scans were obtained for 185 patients. The L3 vertebra was identified manually and machine learning software was used to assist skeletal muscle segmentation. Cross- sectional area of skeletal muscle was obtained and normalised to patients’ height. This provided skeletal muscle index (SMI). Sarcopenia was defined using sex- specific international consensus SMI definitions of <39 cm²/m² in women and <55 cm²/m² in men. Associations between pre-treatment sarcopenia and OS and PFS were analysed using univariate and multivariate Cox proportional hazards models and Kaplan-Meier (KM) Of 244 patients, 114 (46.7%) were sarcopenic, 71 (29.1%) were non-sarcopenic and 59 (24.2%) had unknown SMI as CT scans were not available. Sarcopenic patients tended to be male (85.1% vs 61.1% in non-sarcopenic patients). No significant differences were observed with respect to age, T stage, smoker status, presence of carcinoma in situ, albumin, haemoglobin, adult comorbidity evaluation-27, World Health Organisation Performance Status (WHO PS), hydronephrosis, neutrophil count, lymphocyte count, tumour stage and provision of neoadjuvant chemotherapy. Median OS and PFS were 40 (interquartile range [IQR] 23.8 – 62) and 32 (IQR 14 - 54.3) months respectively (see figure 1). Univariate analysis showed no association between sarcopenia and OS or PFS. On multivariate analysis, WHO PS, hydronephrosis and neutrophil count were associated with worse OS and PFS. radiotherapy (GemX). Material and Methods curves. Results

Conclusion Sarcopenia is not associated with worse OS or PFS in bladder cancer patients treated with concurrent chemoradiotherapy.