Immune checkpoint inhibitors for patients acquired resistance to tyrosine kinase inhibitors with EGFR mutated non-small cell lung cancer: A multicenter retrospective study

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 UMI28989. 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.