ESTRO 37 Abstract book

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ESTRO 37

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 carcinoma was conducted. Patients were randomized to receive SBRT either prior to the first cycle (arm A) or prior to the third cycle (arm B) of pembrolizumab. SBRT was delivered in 3 fractions of 8 Gy to the largest lesion that could be irradiated safely. Secondary outcomes include overall objective response rate according to RECIST v1.1 and immune related response criteria (irRC), overall survival, progression-free survival and systemic immune response as assessed via liquid biopsies throughout the trial. Results 18 patients were enrolled and received trial treatment. Treatment-related adverse events grade 1-2 occurred in 6 out of 9 patients in arm A and in 9 out of 9 patients in arm B. No grade 3-5 treatment-related adverse events and no dose-limiting toxicities occurred. Treatment- related adverse events included pruritus (n=7), thyroid function test abnormalities (n=8), lymphopenia (n=5), maculopapular rash (n=3), fatigue (n=3), diarrhea (n=3), radiodermatitis (n=1), arthralgia (n=1) and edema (n=1). In arm A all patients experienced progressive disease as best overall response as per RECIST v1.1 and irRC. In arm B an objective response rate of 44,4% was noted, with 3 partial responses and 1 complete response as per RECIST v1.1 and irRC; all other patients experienced progressive disease. Median progression-free survival was 11,9 and 11,1 weeks in arm A and B respectively. Median overall survival was 17,9 weeks in arm A and not reached in arm B. Conclusion We conclude that the combination of pembrolizumab with SBRT is feasible and safe in patients with metastatic urothelial carcinoma. To further explore the benefit of this combination, future phase II and III clinical trials should administer SBRT prior to the third cycle of pembrolizumab.

points 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. 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

Debate: This house believes that stereotactic radiosurgery will replace whole brain radiotherapy in patients with ten brain metastases

SP-0683 Stereotactic radiosurgery for patients with 10 or more brain metastases M. Yamamoto 1 1 Yamamoto Masaaki, Department of Neurosurgery, Hitachi-naka, Japan Abstract text The JLGK0901 study showed the non-inferiority of stereotactic radiosurgery (SRS) alone as initial treatment for 5-10 as compared to 2-4 brain metastases (BMs) in