ESTRO 38 Abstract book

S116 ESTRO 38

Combinations. Nature Rev Clin Oncol, 2016. doi: 10.1038/nrclinonc.2016.79. SP-0230 Radiation and TKIs - what is the 2019 evidence? C. Belka 1 1 University Hospital- LMU Munich, Department of Radiation Oncology, Munich, Germany SP-0231 Radiotherapy in combination with DNA damage response inhibitors in 2019: are we any closer to clinical benefit? A. Chalmers 1 1 Inst. of Cancer Sciences-Univ. Glasgow, Department of Clinical Oncology, Glasgow, United Kingdom Abstract text Clinical evaluation of radiotherapy in combination with inhibitors of the DNA damage response has been underway for several years now and, while knowledge about effects on normal tissue toxicity is accruing, evidence of improved tumour control is still awaited. PARP inhibitors are the most advanced class of agents to be tested in the clinic, and this presentation will summarise the key observations made in the early phase trials that have been conducted to date. I will also consider how progress might have been accelerated if more efficient clinical trial designs had been adopted. Inhibitors of additional DNA damage response proteins are also entering the clinic, both as single agents and in combination with radiotherapy, and pre-clinical data indicates that some of these may be more potent radiosensitizers than PARP inhibitors. After summarising the pre-clinical findings, I will review the key clinical trials and consider how we might select patients for particular radiation-DDRi combinations. Finally I will present some novel clinical trial designs that might enable us to make more rapid progress in this area. SP-0232 Cost-estimate models for radiation-drug combinations A.H. Ree 1 1 Akershus University Hospital, Department of Oncology, Lørenskog, Norway Abstract text Programs within precision cancer medicine are being conducted at an increasing number of cancer centers internationally, in line with recommendations from multiple governmental and independent initiatives. A common objective for such activities is the integration of existing resources and new investments in technologies and therapies that reside in the industrial, regulatory, academic, and clinical practice sectors. The presentation will discuss modeling of costs of the required infrastructure to conduct precision medicine studies with rational radiation-drug combinations in the public health services. The model compares cost-per-patient figures for: - Radiation alone (the benchmark) -Radiation combined with biomarker-agnostic use of a given drug (combination A) -Radiation combined with molecularly matched medication (combination B) The estimations include costs for: -The medication -Outpatient clinic visits -Admission from adverse events -The biomarker-based diagnostic procedures The input parameters comprise: -A set of given diagnosis-related-group indicators -Wholesale drug prices, including costs for required oncology nursing to administer intravenous drugs Abstract not received

microsatellite regions in the genome. Patients with mismatch repair deficient tumours (dMMR) have a high overall response rate to PD-1/PD-L1 blockade. TMB measurement is highly dependent on the method and a clear cut-off has not yet been defined. However, the likelihood that TMB will become a standard test is high. The diversity of the T-cell repertoire can be measured by DNA sequencing of the TCR Vβ genes. The presence of a restricted or uneven TCR repertoire measured in the peripheral blood had a negative impact on survival in patients with melanoma or bladder cancer treated with IO. At present, this is still a highly experimental technique. As the inflammatory status of the tumor micro- environment is also determining the response to IO, markers like lactate dehydrogenase (LDH), CRP, vascular endothelial growth factor (VEGF) and soluble CD25 are associated with response to anti-CTLA-4 and PD-1/PD-L1 blockade in advanced melanoma. However, more work is needed to validate these findings and to establish cut-off values that would make these clinically relevant. Baseline neutrophil-to-lymphocyte ratios and relative eosinophil count are associated with response to IO, but none of these have an accuracy which is high enough to be useful in the clinic. Finally, circulating tumor DNA seems to be a very sensitive marker that allows to detect both tumor growth as well as response far before imaging does. It is likely that the coming years circulating biomarkers will become available and more specific in order to change the landscape of IO to make it more efficient for more patients. Abstract text Radiotherapy is a fundamental component of treatment for the majority of patients with cancer. In recent decades, technological advances have enabled patients to receive more targeted doses of radiation to the tumour, with sparing of adjacent normal tissues. There is great potential for new drug-radiotherapy treatment strategies to improve clinical outcomes for patients. Novel combinations from the most relevant preclinical models of cancer biology and immune-oncology should be prioritised for rapid advancement to the clinic. Early and frequent communication between multiple stakeholders including industry, academia, regulatory agencies and patient advocates is essential to generate sufficient numbers of clinical trials and to increase the rate of progress. Intelligent trial designs are required to increase the number of studies which efficiently meet their primary outcomes. Endpoints including local control, organ preservation and patient-reported outcomes may demonstrate clinical benefit and are of specific relevance to clinical trials of new drug-radiotherapy combinations. In this talk, I will discuss barriers that have been identified to the development of new drug- radiotherapy combinations, and solutions to increase the number of clinical trials. Interested readers are recommended to read the review article published by the NCRI CTRad Academia-Pharma Joint Working Group: Sharma, R.A., et al., NCRI CTRad Academia- Pharma Joint Working Group. (2016). Clinical Development of New Drug-Radiotherapy Symposium: Radiation-drug combinations on the 2019 horizon SP-0229 Barriers and solutions to increase the number of clinical trials of new drug-radiotherapy combinations R. Sharma 1 1 UCL Cancer Institute, University College London, London, United Kingdom