1145P Atezolizumab and stereotactic body radiotherapy in patients with advanced non-small cell lung cancer: The ComIT-1 trial

Abstract

The emerging use of immune checkpoint inhibitors has transformed the treatment landscape of metastatic non-small cell lung cancer (NSCLC). However, challenges remain to increase the number of patients achieving durable clinical responses to these drugs, and to help monitor the treatment effect. In this phase II trial, we investigated the toxicity, systemic responses and circulating tumor DNA (ctDNA) responses in patients with advanced NSCLC treated with atezolizumab and stereotactic body radiotherapy (SBRT). Patients with metastatic NSCLC previously treated with a platinum doublet were included. SBRT (3 doses of 6 Gy) was given with concurrent atezolizumab 1200 mg every three weeks until no clinical benefit, intolerable toxicity, or a maximum of two years. Safety and clinical responses were registered. Plasma collected at baseline, during treatment and at progression was analyzed by next-generation sequencing using a 52-gene panel. We examined the relationship between longitudinal changes in ctDNA levels quantified using the allele frequency (AF) of lung cancer-associated somatic mutations, and radiographic responses for each patient. 21 patients were enrolled, of whom 15 with programmed death-ligand 1 (PD-L1) negative tumors. Grade 3 treatment-related adverse events were reported in three patients, leading to permanent discontinuation of treatment in one. No patients experienced grade 4–5 toxicity. Median overall survival time was still not reached at data cut-off. As best overall response, four patients had a partial response (PR), eight had stable disease (SD) and five had progressive disease (PD). Eight patients, including six with PD-L1 negative tumors, were on treatment for more than 12 months. ctDNA was detectable at baseline in 11 plasma samples. A rapid decline in ctDNA to <30% of baseline levels was seen for three patients, two of them radiographic responders and one considered clinically benefiting from therapy for almost one year. Atezolizumab was safely administered concomitant with SBRT, but further trials are needed to assess the efficacy of this combination. ctDNA holds potential as a dynamic biomarker in lung cancer patients receiving immune checkpoint inhibitors.