[en] INTRODUCTION: Durvalumab is a selective, high-affinity human IgG1 monoclonal antibody that blocks programmed cell death ligand-1 (PD-L1) binding to PD-1. Here we report safety and clinical activity in the non-small cell lung cancer (NSCLC) cohort of a Phase 1/2 trial that included multiple tumor types (Study 1108; NCT01693562). METHODS: Patients with stage IIIB-IV NSCLC (squamous or nonsquamous) received durvalumab 10 mg/kg q2w for 12 months or until confirmed progressive disease or unacceptable toxicity. Primary objectives were safety and antitumor activity. Tumoral PD-L1 expression was assessed using the VENTANA SP263 Assay. Responses were assessed by blinded independent central review (RECIST v1.1). Adverse events were graded according to NCI CTCAE v4.03. RESULTS: Of 304 patients, 79.0% were previously treated. Confirmed objective response rate was 21.8% in patients with >/=25% PD-L1 expression and 6.4% in those with <25%; 25.9% in first-line patients and 12.7% in previously treated patients; 14.0% in squamous and 16.7% in nonsquamous disease. Median OS was 12.4 months and median PFS was 1.7 months; both were numerically longer in the PD-L1 >/=25% group than in the PD-L1 <25% group (OS 16.4 vs 7.6 months; PFS 2.6 vs 1.4 months). Treatment-related adverse events occurred in 57.2%, were Grade 3/4 in 10.2%, and led to discontinuation in 5.6%. One patient (0.3%) died of treatment-related pneumonia with underlying pneumonitis. CONCLUSIONS: Durvalumab was clinically active irrespective of histology in this mostly pretreated population, with a manageable safety profile. Response rates and survival appeared to be enhanced in patients with greater tumoral PD-L1 expression.
Disciplines :
Oncology
Author, co-author :
Antonia, Scott J.
Balmanoukian, Ani
Brahmer, Julie
Ou, Sai-Hong I.
Hellmann, Matthew D.
Kim, Sang-We
Ahn, Myung-Ju
Kim, Dong-Wan
Gutierrez, Martin
Liu, Stephen V.
Schoffski, Patrick
Jager, Dirk
Jamal, Rahima
Jerusalem, Guy ; Université de Liège - ULiège > Département des sciences cliniques > Oncologie
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