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. 2023 Jan 10;4(3):100459.
doi: 10.1016/j.jtocrr.2022.100459. eCollection 2023 Mar.

Osimertinib in NSCLC With Atypical EGFR-Activating Mutations: A Retrospective Multicenter Study

Jingran Ji  1   2 , Jacqueline V Aredo  3 , Andrew Piper-Vallillo  4 , Laura Huppert  5 , Julia K Rotow  6 , Hatim Husain  7 , Susan Stewart  2 , Rosemary Cobb  4 , Heather A Wakelee  3 , Collin M Blakely  5 , Melisa L Wong  5 , Matthew A Gubens  5 , Mohammad H Madani  2 , Subba R Digumarthy  4 , Caroline McCoach  5 , Zofia Piotrowska  4 , Joel W Neal  3 , Jonathan W Riess  2
Affiliations

Osimertinib in NSCLC With Atypical EGFR-Activating Mutations: A Retrospective Multicenter Study

Jingran Ji et al. JTO Clin Res Rep. .

Abstract

Introduction: EGFR mutations drive a subset of NSCLC. Patients harboring the common EGFR mutations, deletion of exon 19 and L858R, respond well to osimertinib, a third-generation tyrosine kinase inhibitor. Nevertheless, the effect of osimertinib on NSCLC with atypical EGFR mutations is not well described. This multicenter retrospective study evaluates the efficacy of osimertinib among patients with NSCLC harboring atypical EGFR mutations.

Methods: Patients with metastatic NSCLC treated with osimertinib, harboring at least one atypical EGFR mutation, excluding concurrent deletion of exon 19, L858R, or T790M mutations, from six U.S. academic cancer centers were included. Baseline clinical characteristics were collected. The primary end point was the time to treatment discontinuation (TTD) of osimertinib. Objective response rate by the Response Evaluation Criteria in Solid Tumors version 1.1 was also assessed.

Results: A total of 50 patients with NSCLC with uncommon EGFR mutations were identified. The most frequent EGFR mutations were L861Q (40%, n = 18), G719X (28%, n = 14), and exon 20 insertion (14%, n = 7). The median TTD of osimertinib was 9.7 months (95% confidence interval [CI]: 6.5-12.9 mo) overall and 10.7 months (95% CI: 3.2-18.1 mo) in the first-line setting (n = 20). The objective response rate was 31.7% (95% CI: 18.1%-48.1%) overall and 41.2% (95% CI: 18.4%-67.1%) in the first-line setting. The median TTD varied among patients with L861Q (17.2 mo), G719X (7.8 mo), and exon 20 insertion (1.5 mo) mutations.

Conclusions: Osimertinib has activity in patients with NSCLC harboring atypical EGFR mutations. Osimertinib activity differs by the type of atypical EGFR-activating mutation.

Keywords: Atypical EGFR mutation; G719X; L861Q; Non–small cell lung cancer; Osimertinib.

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Figures

Figure 1
Figure 1
Kaplan-Meier analysis of time to discontinuation of osimertinib in (A) overall population and in (B) first- and subsequent-line settings.
Figure 2
Figure 2
Best percentage change in target lesions among patients with atypical EGFR mutations. The upper dashed line marks the threshold for progressive disease at 20% increase in the sum of the longest diameter of target lesions. The lower dashed line at −30% marks the threshold for partial response.
Figure 3
Figure 3
Kaplan-Meier analysis of time on osimertinib in the overall population when comparing patients harboring L861Q mutations (green line) versus those harboring G719X mutations (blue line).
See this image and copyright information in PMC

References

    1. Shigematsu H., Lin L., Takahashi T., et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst. 2005;97:339–346. - PubMed
    1. Kosaka T., Yatabe Y., Endoh H., Kuwano H., Takahashi T., Mitsudomi T. Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications. Cancer Res. 2004;64:8919–8923. - PubMed
    1. Hsu W.H., Yang J.C., Mok T.S., Loong H.H. Overview of current systemic management of EGFR-mutant NSCLC. Ann Oncol. 2018;29(suppl 1):i3–i9. - PubMed
    1. Riess J.W., Gandara D.R., Frampton G.M., et al. Diverse EGFR Exon 20 insertions and co-occurring molecular alterations identified by comprehensive genomic profiling of NSCLC. J Thorac Oncol. 2018;13:1560–1568. - PMC - PubMed
    1. Chiu C.H., Yang C.T., Shih J.Y., et al. Epidermal growth factor receptor tyrosine kinase inhibitor treatment response in advanced lung adenocarcinomas with G719X/L861Q/S768I mutations. J Thorac Oncol. 2015;10:793–799. - PubMed