Clinical Activity, Tolerability, and Long-Term Follow-Up of Durvalumab in Patients With Advanced NSCLC

Scott J. Antonia, Ani Balmanoukian, Julie Brahmer, Sai Hong I. Ou, Matthew D. Hellmann, Sang We Kim, Myung Ju Ahn, Dong Wan Kim, Martin Gutierrez, Stephen V. Liu, Patrick Schöffski, Dirk Jäger, Rahima Jamal, Guy Jerusalem, Jose Lutzky, John Nemunaitis, Luana Calabrò, Jared Weiss, Shirish Gadgeel, Jaishree BhoslePaolo A. Ascierto, Marlon C. Rebelatto, Rajesh Narwal, Meina Liang, Feng Xiao, Joyce Antal, Shaad Abdullah, Natasha Angra, Ashok K. Gupta, Samir N. Khleif, Neil H. Segal

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Durvalumab is a selective, high-affinity human immunoglobulin G1 monoclonal antibody that blocks programmed cell death ligand 1 (PD-L1) binding to programmed death 1. Here we report safety and clinical activity in the NSCLC cohort of a phase I/II trial that included multiple tumor types (Study 1108; NCT01693562). Methods: Patients with stage IIIB–IV NSCLC (squamous or nonsquamous) received durvalumab 10 mg/kg every 2 weeks 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 (Response Evaluation Criteria in Solid Tumors v1.1). Adverse events were graded according to National Cancer Institute's Common Terminology Criteria for Adverse Events (v4.03). Results: Of 304 patients, 79.0% were previously treated. Confirmed objective response rate was 21.8% in patients with greater than or equal to 25% PD-L1 expression and 6.4% in those with less than 25%; 25.9% in first-line patients and 12.7% in previously treated patients; and 14.0% in squamous and 16.7% in nonsquamous disease. Median overall survival was 12.4 months and median progression-free survival was 1.7 months; both were numerically longer in the PD-L1 greater than or equal to 25% group than in the PD-L1 less than 25% group (overall survival 16.4 versus 7.6 months, respectively; progression-free survival 2.6 versus 1.4 months, respectively). 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.

Original languageEnglish
Pages (from-to)1794-1806
Number of pages13
JournalJournal of Thoracic Oncology
Volume14
Issue number10
DOIs
Publication statusPublished - Oct 1 2019

Keywords

  • Durvalumab
  • Efficacy
  • Immunotherapy
  • NSCLC
  • Safety

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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