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J. Thorac. Oncol., Available online 15 February 2022 | https://doi.org/10.1016/j.jtho.2022.01.012 Osimertinib Plus Durvalumab in Patients With EGFR-Mutated, Advanced NSCLC: A Phase 1b, Open-Label, Multicenter Trial

Myung-Ju Ahn MD, PhD^a,Byoung Chul Cho MD, PhD^b, Xiaoling Ou PhD^c, Andrew Walding MSc^d, Angela W. Dymond MSc^e, Song Ren PhD^f, Mireille Cantarini MbChB^g, Pasi A. Jänne MD, PhD^h

^aDepartment of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
^bYonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
^cEarly Clinical Development, AstraZeneca, Cambridge, United Kingdom
^dLate Development Oncology, AstraZeneca, Cambridge, United Kingdom
^eCovance Clinical Research Unit Limited, Leeds, United Kingdom
^fClinical Pharmacology & Quantitative Pharmacology, AstraZeneca, Gaithersburg, Maryland
^gOncology R&D, AstraZeneca, Macclesfield, United Kingdom
^hLowe Center for Thoracic Oncology, Robert and Renée Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts

^*Corresponding author.

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. Nevertheless, 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 antitumor 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 or 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.

논문정보

형식Research article
게재일2022년 02월 (BRIC 등록일 2022-03-31)
연구진국내(교신)+국외 연구진
분야 의약학 > 종양의학

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