ESTRO 2020 Abstract Book

S641 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.

Conclusion Concurrent NIVO plus SBRT appears to be well tolerated, without increased rates of severe toxicity. Definitive data of efficacy and toxicities of immunotherapy in combination with radiotherapy are not yet mature, but will be hopefully provided soon. PO-1218 Oligo Metastatic renal cell carcinoma: SBRT, if, when and how? G. Marvaso 1 , G. Corrao 1 , O. Oneta 1 , S.G. Gugliandolo 1 , M. Pepa 1 , A. Cecconi 1 , S. Gandini 2 , G. Piperno 1 , M. Cossu Rocca 3 , E. Verri 3 , G. Aurilio 3 , F. Corso 2 , D. Cullurà 3 , E. Rondi 4 , S. Vigorito 4 , F. Nolè 3 , R. Orecchia 5 , B.A. Jereczek- Fossa 1 1 IEO- European Institute of Oncology IRCCS, Division of Radiotherapy, Milan, Italy ; 2 IEO- European Institute of Oncology IRCCS, Department of Experimental Oncology, Milan, Italy ; 3 IEO- European Institute of Oncology IRCCS, Division of Medical Oncology, Milan, Italy ; 4 IEO- European Institute of Oncology IRCCS, Unit of Medical Physics, Milan, Italy ; 5 IEO- European Institute of Oncology IRCCS, Scientific Direction, Milan, Italy Purpose or Objective Renal cell carcinoma (RCC) have traditionally been considered radioresistant with a limited role for conventional fractionation as a local approach but since the appearance of stereotactic body radiation therapy (SBRT), radiotherapy (RT) has been increasingly employed in the management of metastatic RCC (mRCC). The aim of this study was to evaluate the role of SBRT for synchronous and metachronous oligo-metastatic RCC patients in terms of local control, delay of systemic treatment, overall Monocentric retrospective data collection from a single institution was performed. The inclusion criteria were as follows: (1) oligo-recurrent or oligo-progressive disease (less than 5) in mRCC patients after local surgery or during survival and toxicity. Material and Methods