ESTRO 2020 Abstract book

S464 ESTRO 2020

SP-0760 Immunotherapy and (chemo)radiotherapy in Stage III NSCLC Y. Lievens Ghent University Hospital, Ghent, Belgium

Joint Symposium: ESTRO-IASLC: Combined radiotherapy and immunotherapy in NSCLC

Abstract not receieved

SP-0758 The immune microenvironment in lung cancer - impact on effect of combined radiotherapy and immunotherapy? Å. Helland 1 1 Institute of Cancer Research, The Cancer Clinic, Oslo, Norway Abstract text Lung cancer is a common disease, with a poor prognosis. During the past decade, immune checkpoint inhibitors have been introduced in the treatment of non-small cell lung cancer, inducing durable responses in a subset of patients. As of yet, our understanding about the differences in responses is sparse. High PDL1 expression levels and mutational burden seems to increase likelihood of responses, but also patients with low PDL1 expression and low tumour mutational burden can experience durable responses. The immune microenvironment is now studied elucidating factors influencing the responses to immune checkpoint inhibition. Aiming at increasing the proportion of lung cancer patients benefitting from checkpoint inhibition, efforts are being made to combine checkpoint inhibitors with other therapeutics. Stereotactic radiotherapy is one such appealing option for combination, with the idea being to induce immunogenic cell death, introducing tumour antigens into circulation and inducing an inflammatory signature. In a series of lung cancer patients, we have analysed tumour tissue by RNA expression analyses, focusing on the immune microenvironment. Gene expression was assessed in 399 surgically derived non-small cell lung cancer samples and 47 samples from normal lung, using Agilent microarray and RNA sequencing. In addition, we have investigated how the cytokine levels in serum samples vary during radiotherapy in patients with non-small cell lung cancer. Concentration levels of selected cytokines and MMPs in serum samples were evaluated by multiplex bioassays (BioRad). Lastly, we have investigated patients treated with a combination of stereotactic radiotherapy and an immune check-point inhibitor. In the expression analyses, tumors with an active immune microenvironement were found in both adenocarcinomas (AD) and squamous cell carcinomas(SCC). The immunoscore was calculated for the histological subgroups analysed, and correlated to survival. The serum levels of some cytokines and MMPs differed significantly during the course of radiotherapy. In a clinical series of patients treated with a combination of a check point inhibitor and stereotactic radiotherapy, analyses of the tumour microenvironment is underway. The immunological microenvironment is important for responses to immunotherapy. In patients with non-small cell lung cancer, radiotherapy induces systemic changes in the inflammatory / immunological environment, which may influence response to other treatment. SP-0759 Immunotherapy approaches to advanced lung cancer TBC

SP-0761 Combining immunotherapy and thoracic radiotherapy in SCLC S. Senan 1 1 Amsterdam University Medical Center, Radiation oncology, Amsterdam, The Netherlands Abstract text Extensive SCLC The prognosis of patients presenting with an extensive SCLC remains poor despite standard chemotherapy and the use of prophylactic cranial irradiation. A pooled meta-analysis of 3 randomized clinical studies reported that consolidation thoracic radiotherapy significantly improved the progression-free survival, and reduced thoracic failures [Rathod S, EJC 2019]. However, no significant benefits in overall survival were observed with consolidation thoracic radiotherapy (HR 0.88, 95% CI 0.66-1.18). Two randomised clinical studies in patients with extensive SCLC have evaluated the combination of anti-PD-L1 antibodies with chemotherapy versus chemotherapy alone. Both the IMpower 133 study evaluating atezolizumab [Horn L, NEJM 2018] and the CASPIAN study evaluating durvalumab [Pas-Arez L, Lancet 2019] included similar patient populations and reported similar adverse events. Both studies had explicitly excluded the use of planned thoracic radiotherapy, and both reported statistically significant improvements in overall survival, although the benefits were clinically modest. These findings have led to approval by the United States FDA for atezolizumab in patients with previously untreated extensive-stage SCLC, and the use of durvalumab is under priority review at the FDA. The feasibility of incorporating concurrent thoracic radiation with a PD-1 checkpoint inhibitor (pembrolizumab) after induction chemotherapy for extensive SCLC, has been reported as feasible [Welsh J, JTO 2019]. Future studies evaluating thoracic radiotherapy in the era of immune checkpoint inhibitors will have to address factors such as disease load (limited volume vs truly extensive disease), the timing of thoracic radiotherapy (sequential vs concurrent) and optimal radiation doses. No biomarkers that could identify patients who are likely to benefit from immune checkpoint inhibitors have been identified. Similarly, the proposed new nomenclature for SCLC subtypes, defined by relative expression of four key transcription regulators [Rudin CM, Nat Rev Med 2018], remains to be studied in trials. Limited SCLC The standard of care in patients with limited stage SCLC is concurrent chemo-radiotherapy, followed by prophylactic cranial irradiation. The role of immune checkpoint inhibitors is an active area of research. Randomized trials evaluating these agents in the consolidation setting after completion of chemo- radiotherapy include NCT02046733 (ipilimumab- nivolumab), NCT03540420 (atezolizumab) and NCT03703297 (durvalumab +/-tremelimumab). Trials evaluating checkpoint inhibitors concurrently with thoracic chemoradiotherapy include NCT03509012 (durvalumab +/- tremelimumab), NCT02402920 (pembrolizumab), NCT03585998 (durvalumab) and NCT03811002 (atezolizumab).

Abstract not received