Abstract Book

S357

ESTRO 37

SP-0681 Clinical Trials Development of Rational Radiotherapy and Immunotherapy Combinations: Prospects and Results F. Herrera 1 1 Centre Hospitalier Universitaire Vaudois, Department of Radiation Oncology, Lausanne Vaud, Switzerland Abstract text The immunomodulatory properties of RT offer important opportunities toward the development of rational combinations with immunotherapy, aiming to maximize local tumor control and eliminate the potential for systemic metastases. However, a considerable amount of work is still required to fully understand how to develop effective combinations of immunotherapeutics and radiation. This talk will review the current status of clinical trials combining radiation and immunotherapy in three main clinical scenarios: 1) Immune therapy is added to hypofractionated RT. The clinical goal here is mainly to reduce distant failures by capitalizing on the in situ vaccination effect of RT coupled to the local and systemic effects of immune therapy. 2) Immune therapy is added to standard-of-care chemo-RT. The clinical goal of adding immune therapy here is to enhance the efficacy of chemo-RT locally and reduce distant failures by building local and systemic synergies between RT and immune modulation, ultimately prolonging progression- free survival and, hopefully, cure rates. 3) Radiation as a biological response modifier to immunotherapy. The clinical goal here is to maximize the efficacy of immune therapy against specific tumor deposits. Each of these conditions requires careful understanding of the biological effects of each therapeutic component. We will provide examples of pre-clinical models that mirror the desired clinical goals as well as results from ongoing clinical trials. The intersection between immunotherapy and radiation therapy is widening and requires thinking outside the box. OC-0682 Phase 1 trial of pembrolizumab with SBRT in metastatic urothelial carcinoma N. Sundahl 1 , S. Rottey 2 , K. Decaestecker 3 , P. De visschere 4 , D. De maeseneer 2 , D. Reynders 5 , A. Meireson 6 , E. Goetghebeur 5 , V. Fonteyne 7 , S. Verbeke 8 , L. Brochez 6 , P. Ost 7 1 university hospital ghent, radiation oncology, gent, belgium 2 university hospital ghent, medical oncology, ghent, belgium 3 university hospital ghent, urology, ghent, belgium 4 university hospital ghent, radiology, ghent, belgium 5 ghent university, department of applied mathematics- computer science and statistics, ghent, belgium 6 university hospital ghent, dermatology and dermatology research unit, ghent, belgium 7 university hospital ghent, radiation oncology, ghent, belgium 8 university hospital ghent, pathology, ghent, belgium Purpose or Objective Pembrolizumab is current standard for second line treatment in patients with metastatic urothelial carcinoma after progression on platinum-based chemotherapy. However, with a response rate of 21.1%, the majority of patients do not respond to this treatment. Preclinical and early clinical data indicate that the addition of radiotherapy could work synergistically and raise response rates. We report the results of the first prospective trial that combined anti- PD1 treatment with radiotherapy. Material and Methods A prospective phase I trial to assess the dose limiting toxicity of the combination of pembrolizumab (200 mg intravenously, every 3 weeks) and stereotactic body radiotherapy (SBRT) in patients with metastatic urothelial

of adaptive antitumor immunity. It has recently been shown that the inhibition of immune inhibitory checkpoints synergizes with ionizing radiation. Hypoxia is one of the key factors influencing clinical outcome after radiotherapy responsible for reduced local control that will influence overall survival, as may the hypoxic conditions by increasing malignant progression. The immune contexture of tumors might be correlated with outcome after irradiation. The purpose of tumor immunotherapy is based on the principle that reversal of tolerance to immunogenic tumors would be able to activate an immune response against tumor cells. The importance of the immune component into the process of tumor response to radiation offers novel opportunities for therapeutic interventions. Recently, novel insights regarding the pivotal role of the interferon response for both tumor local and abscopal response to radiotherapy provide a potential link between the DNA damage repair and signaling pathways and the induction of anti tumor immunity by radiotherapy. Preclinical data underscoring the potential of immune therapies as amplifiers of both the local and systemic anti tumor effect of radiotherapy do suggest the role of these agents for clinical transfert. However, manjor challenges remain such as optimizing the dose and fractionation, defining the best drug- irradiation scheduling and also the best type of immunological agent, the existence of a normal tissue versus tumor differential index. SP-0680 Toxicity profile of immune checkpoint inhibitors and combined radiotherapy treatment P.C. Lara Jimenez 1 1 Hospital Universitario de Gran Canaria Dr. Negrín, Academic Physics, Las Palmas de Gran Canaria- Ca, Spain Abstract text Immune chek point inhibitors (ICIs) are drugs that block the constitutive regulatory supressor mechanisms designed to prevent “autoinmune attacks” from the immune sytem, to normal tissue. These mechanisms are constitutive either in lymhocytes (CTL4/ PD-1/PD-L1) but also in tumour cells (PD-1/PDL-1). Therefore by “supressing the supressors” (using anti CTL4 , Anti PD-1 or anti PD-L1 antibodies) the immune system is free of the regulatory supressive signals and results reinvigorated to respond to antigen stimulii. Targeting these checkpoints in cancer patients had led to long-lasting tumour responses. But, these new immunotherapies also generate dysimmune toxicities, called immune-related adverse events (IRAEs) that mainly involve the gut, skin, endocrine glands, liver, and lung . In view of their evident clinical efficacy, anti-CTLA-4 and anti-PD-1 antibodies are entering in the routine oncological practice, and patients treated with these drugs will increase dramatically in the near future. When IRAEs appear dose reduction, halt drug administration, systemic corticosteroids or in severe cases, anti-TNF α therapy should be taken in to account. SBRT/SRS autovaccination- mediated antigen presentation and PD-1 RT-induced overexpression could result in an increased abscopal effect and better survival as the immune system is reinvigorated by the ICI-mediated activation. Combinations of SBRT/SRS and ICI seems to be safe according to the few trials available. Oncologist must know the mechanism behind IRAEs and must be ready to detect and manage these new types of adverse events.