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

Myung Ju Ahn, Byoung Chul Cho, Xiaoling Ou, Andrew Walding, Angela W. Dymond, Song Ren, Mireille Cantarini, Pasi A. Jänne

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)718-723
Number of pages6
JournalJournal of Thoracic Oncology
Volume17
Issue number5
DOIs
Publication statusPublished - 2022 May

Bibliographical note

Publisher Copyright:
© 2022 International Association for the Study of Lung Cancer

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine

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