Osimertinib Plus Durvalumab in Patients With EGFR-Mutated, Advanced NSCLC: A Phase 1b, Open-Label, Multicenter Trial

J Thorac Oncol. 2022 May;17(5):718-723. doi: 10.1016/j.jtho.2022.01.012. Epub 2022 Feb 15.

Abstract

Introduction: EGFR tyrosine kinase inhibitors (TKIs) are recommended for EGFR-mutated NSCLC treatment. EGFR activation up-regulates programmed death-ligand 1 expression and other immunosuppressive factors in NSCLC, causing immune microenvironment remodeling. Osimertinib (an EGFR TKI) plus durvalumab (programmed death-ligand 1 blockade) was evaluated in the TATTON study (NCT02143466).

Methods: This open-label, phase 1b study enrolled patients with advanced EGFR-mutated NSCLC. In part A, patients who had progressed on a previous EGFR TKI received osimertinib (80 mg once daily) plus durvalumab 3 or 10 mg/kg every 2 weeks. In part B, patients received first-line osimertinib plus durvalumab 10 mg/kg every 2 weeks. However, part B enrollment was terminated early owing to an increased incidence of interstitial lung disease (ILD)-related adverse events (AEs). Safety (primary objective) and preliminary anti-tumor activity determined by objective response rate (ORR), best overall response, duration of response (DOR), and progression-free survival were evaluated.

Results: Before enrollment termination, 23 and 11 patients received treatment across parts A and B, respectively. The most common AEs across parts A and B were as follows: diarrhea (50%), nausea (41%), and decreased appetite (35%). A total of 12 patients (35%) reported ILD-related AEs (lung disorder, ILD or pneumonitis). In part A, ORR was 43% (95% confidence interval [CI]: 23-66); median DOR was 20.4 months. In part B, ORR was 82% (95% CI: 48-98), median DOR was 7.1 months, and median progression-free survival was 9.0 months (95% CI: 3.5-12.3).

Conclusions: This study highlighted a potential risk of ILD-related AEs when combining osimertinib with durvalumab. Further research looking to combine EGFR TKIs with immune checkpoint inhibitors should be approached with caution.

Keywords: Durvalumab; EGFR; NSCLC; Osimertinib.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Acrylamides
  • Aniline Compounds / pharmacology
  • Aniline Compounds / therapeutic use
  • Antibodies, Monoclonal
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • ErbB Receptors / genetics
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / metabolism
  • Mutation
  • Protein Kinase Inhibitors / therapeutic use
  • Tumor Microenvironment

Substances

  • Acrylamides
  • Aniline Compounds
  • Antibodies, Monoclonal
  • Protein Kinase Inhibitors
  • durvalumab
  • osimertinib
  • EGFR protein, human
  • ErbB Receptors

Associated data

  • ClinicalTrials.gov/NCT02143466