title: Concurrent irradiation with the anti-programmed cell death ligand-1 immune checkpoint blocker durvalumab: Single centre subset analysis from a phase 1/2 trial.
abstract: 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.
  
  
  
  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]).
  
  
  
  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).
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Antonin
authors.initials: A
authors.lastname: Levy
authors.affiliation: DITEP, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Massard
authors.affiliation: DITEP, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.affiliation: 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.
authors.forename: Eric
authors.initials: E
authors.lastname: Deutsch
mesh_terms: D000230:Adenocarcinoma / Q000556:secondary / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors; D001859:Bone Neoplasms / Q000556:secondary / Q000628:therapy; D001932:Brain Neoplasms / Q000556:secondary / Q000628:therapy; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy; D002295:Carcinoma, Transitional Cell / Q000556:secondary / Q000628:therapy; D059248:Chemoradiotherapy; D003110:Colonic Neoplasms / Q000473:pathology / Q000628:therapy; D018572:Disease-Free Survival; D005134:Eye Neoplasms / Q000473:pathology / Q000628:therapy; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000628:therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000556:secondary / Q000628:therapy; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy; D008207:Lymphatic Metastasis / Q000532:radiotherapy; D008297:Male; D008545:Melanoma / Q000556:secondary / Q000628:therapy; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy*; D016634:Radiosurgery; D020266:Radiotherapy, Conformal; D055752:Small Cell Lung Carcinoma / Q000556:secondary / Q000628:therapy; D000077195:Squamous Cell Carcinoma of Head and Neck; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000628:therapy
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C000613593:durvalumab
keywords: Anti-PD-L1; Immunoradiotherapy; Phase 1; Phase 2; Radiotherapy