Antonin Levy1, Christophe Massard2, Jean-Charles Soria2, Eric Deutsch3. 1. Department of Radiation Oncology, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France; DITEP, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France; INSERM U1030, Molecular Radiotherapy, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France; University Paris Sud, Université Paris-Saclay, F-94270, Le Kremlin-Bicêtre, France. Electronic address: Antonin.LEVY@gustaveroussy.fr. 2. DITEP, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France. 3. Department of Radiation Oncology, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France; DITEP, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France; INSERM U1030, Molecular Radiotherapy, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France; University Paris Sud, Université Paris-Saclay, F-94270, Le Kremlin-Bicêtre, France.
Abstract
PURPOSE: To assess preliminary safety and efficacy results of the anti-programmed cell death ligand-1 (anti-PD-L1) durvalumab in combination with radiotherapy (RT) in an expansion cohort of patients included in a phase 1/2 trial at our institution. PATIENTS AND METHODS: Data from patients who received concurrent palliative RT with durvalumab (10 mg/kg every 2 weeks via intravenous infusion) were analysed in terms of safety (CTCAE v4.0) and efficacy (RECIST v1.1 and tumour growth rate [TGR]). RESULTS: Between 02/2014 and 04/2016, 10 patients received palliative local irradiation of 15 isolated lesions. Most patients (90%) had received one or more prior lines of systemic therapy for advanced disease. The median duration of exposure to durvalumab was 5.2 months with a median delivery of 11 cycles (range, 4-38 cycles). RT (conformal 3D RT, 79% and intracranial stereotactic RT, 21%) was delivered at a median biologically-effective dose of 28 Gy (range, 6-92), in a median number of five fractions (range, 1-10) and over a median duration of 6 d (range, 1-14). Five patients (50%) reported an irradiation-related adverse event (AE) grade (G) 1 or 2 and one patient had two G2 AEs. The most frequently reported AE (3/6) was G2 mucositis. There was no G3 or more RT-related AEs. All AEs were transient, lasted less than one week, and were manageable by standard guidelines. There was no unexpected AE. On 10/15 in-field (IF) evaluable lesions, the objective response (OR) rate was 60% (complete response, 2/10 and partial response, 4/10) and 4/10 stable disease (SD). All evaluated IF lesions had a TGR decrease resulting in a significant decrease in the TGR between the two periods (before versus after RT; p < 0.01). Outfields disease evaluation retrieved 10/14 SD and 4/14 progressive disease (PD). There was no out-field OR, no abscopal effect and no out-field difference between the two periods according to TGR (p = 0.09). CONCLUSION: In this small data set of patients, concurrent palliative RT with the anti-PD-L1 durvalumab was well tolerated. ClinicalTrials.gov number: NCT01693562; EudraCT number: 2012-002206-52.
PURPOSE: To assess preliminary safety and efficacy results of the anti-programmed cell death ligand-1 (anti-PD-L1) durvalumab in combination with radiotherapy (RT) in an expansion cohort of patients included in a phase 1/2 trial at our institution. PATIENTS AND METHODS: Data from patients who received concurrent palliative RT with durvalumab (10 mg/kg every 2 weeks via intravenous infusion) were analysed in terms of safety (CTCAE v4.0) and efficacy (RECIST v1.1 and tumour growth rate [TGR]). RESULTS: Between 02/2014 and 04/2016, 10 patients received palliative local irradiation of 15 isolated lesions. Most patients (90%) had received one or more prior lines of systemic therapy for advanced disease. The median duration of exposure to durvalumab was 5.2 months with a median delivery of 11 cycles (range, 4-38 cycles). RT (conformal 3D RT, 79% and intracranial stereotactic RT, 21%) was delivered at a median biologically-effective dose of 28 Gy (range, 6-92), in a median number of five fractions (range, 1-10) and over a median duration of 6 d (range, 1-14). Five patients (50%) reported an irradiation-related adverse event (AE) grade (G) 1 or 2 and one patient had two G2 AEs. The most frequently reported AE (3/6) was G2 mucositis. There was no G3 or more RT-related AEs. All AEs were transient, lasted less than one week, and were manageable by standard guidelines. There was no unexpected AE. On 10/15 in-field (IF) evaluable lesions, the objective response (OR) rate was 60% (complete response, 2/10 and partial response, 4/10) and 4/10 stable disease (SD). All evaluated IF lesions had a TGR decrease resulting in a significant decrease in the TGR between the two periods (before versus after RT; p < 0.01). Outfields disease evaluation retrieved 10/14 SD and 4/14 progressive disease (PD). There was no out-field OR, no abscopal effect and no out-field difference between the two periods according to TGR (p = 0.09). CONCLUSION: In this small data set of patients, concurrent palliative RT with the anti-PD-L1durvalumab was well tolerated. ClinicalTrials.gov number: NCT01693562; EudraCT number: 2012-002206-52.