507PImmune checkpoint inhibitors for patients acquired resistance to tyrosine kinase inhibitors with EGFR mutated non-small cell lung cancer: A multicenter retrospective study. (24th November 2019)

• Record Type: Journal Article
• Authors: Uenami, T; Mori, M; Shiroyama, T; Nagatomo, I; Ihara, S; Komuta, K; Suzuki, H; Hirashima, T; Kimura, M; Imamura, F
• Is Part Of: Annals of oncology. Volume 30(2019)Supplement 9
• Publication Date: 2019-11-24
• Subjects: Oncology -- Periodicals; 616.992
• DOI: 10.1093/annonc/mdz437.033
• Languages: English
• ISSNs: 0923-7534

Abstract

Abstract: Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) represent a highly effective treatment for advanced non-small-cell lung cancer (NSCLC) with active mutations of the EGFR gene. However, most patients develop acquired resistance to EGFR-TKIs. The T790M mutation has been found to be associated with almost 50% of patients who acquired resistance to first- or second- generation EGFR-TKIs. The role of immune checkpoint inhibitors (ICIs) for patients without a T790M mutation or patients with a T790M mutation who have progressed after T790M inhibitor therapy remains unclear. Methods: We retrospectively evaluated the clinical effects of ICIs for EGFR mutated non- squamous NSCLC patients who were treated after developing resistance to first- or second- generation EGFR-TKIs at five institutions in Japan. Patients treated with EGFR-TKI between May 2016 and October 2018 were enrolled. Patients who used a third-generation EGFR-TKI before using prior generations were excluded. Results: Of the 58 patients identified, 21 were positive for T790M, and all were developing resistance to both third- and prior generation EGFR-TKIs. The objective response and disease control rates for ICIs were 13.8% and 55.2% respectively, and T790M-negative patients had numerically greater responses than T790M-positive patients (16.2% versus 9.5% and 62.1% versus 42.9%, p = 0.70 and p = 0.18, respectively). T790M-negative patients were associated with a clinically meaningfully longer median progression-free survival than were T790M-positive patients (4.4 months versus 1.8 months, p = 0.061). Conclusions: T790M-negative status after development of acquired resistance to EGFR-TKIs tended to be associated with benefit from immunotherapy in this retrospective analysis. Clinical trial identification: UMIN000028989. Legal entity responsible for the study: The authors. Funding: AstraZeneca K. K. Disclosure: F. Imamura: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca. All other authors have declared no conflicts of interest.