EGFR TKI retreatment effective after earlier discontinuation

Although treatment with an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is remarkably effective in patients with non-small-cell lung cancer (NSCLC) with an EGFR activating mutation, resistance eventually catches up. Approximately after 1 year of treatment, resistance against EGFR TKI treatment develops. Another issue in the treatment of NSCLC patients harbouring EGFR mutations occurs when they cannot tolerate anti-EGFR treatment due to toxicity, leading to treatment discontinuation. After treatment discontinuation, either switching to another EGFR inhibitor or drug re-exposure are commonly performed after the adverse event has resolved, but the efficacy of retreatment has not been established.

In the retrospective study by Takahashi et al., patients were investigated who received EGFR TKI (re-) treatment between January 2008 and August 2017. Overall survival, response rate, and time to treatment failure for each administered TKI were assessed, for patients who discontinued EGFR TKI due to progressive disease and patients who discontinued the TKI as a result of AEs [1]. A total of 1,400 patients from 11 institutions were enrolled in this study. Of those, 570 patients received retreatment with EGFR TKI, and 541 were eligible to participate.

As much as 395 patients discontinued initial EGFR TKI treatment because of disease progression. Re-administration of subsequent gefitinib/erlotinib/afatinib in these patients resulted in response rates of 8%/8%/18% and median time to treatment failure of 4.9/3.2/4.3 months, respectively. The median time to retreatment failure for the patients who originally discontinued because of AEs was significantly longer than for the patients who originally discontinued due to progressive disease (10.8 months vs 3.8 months, P<0.0001). In both groups, overall survival was significantly better for patients receiving retreatment with EGFR TKI compared with patients without retreatment (HR 0.256, P< 0.0001 for initial discontinuation due to AEs; HR 0.456, P<0.0001 for initial discontinuation due to progression). It was thus concluded that retreatment with EGFR TKI was effective for both patient groups.

1.  Takahashi K, et al. P2.14-11. WCLC 2019.

Posted on 8 November 20195 March 2021