498P - An observational retrospective study to evaluate the incidence of acquired EGFR T790M resistance in NSCLC patients with EGFR mutation following progression after at least one prior EGFR TKI treatment in Taiwan: ARISE study

Background

In Taiwan, gefitinib, erlotinib, and afatinib are all prescribed as the first-line therapy in NSCLC patients with EGFR sensitizing mutation. Although EGFR mutation-positive patients had favorable treatment response of EGFR TKIs, acquired resistance eventually developed, especially acquired EGFR T790M mutation. The 3^rd-generation EGFR TKI, osimertinib, has been approved effectiveness for patients with acquired T790M formation after 1^st-and 2^nd-generation EGFR TKIs treatment. However, it is unclear whether the incidence of acquired T790M resistance differs as a result of the choice of the first-line EGFR TKI therapy. This study aimed to evaluate the association between the prior EGFR TKI therapy and the incidence of acquired T790M resistance in NSCLC patients who have progressed on EGFR TKI therapy.

Methods

Eligibility included NSCLC patients who had re-biopsy results for testing EGFR T790M mutation from 7 medical centers in Taiwan after June 1, 2013. The primary endpoint is to compare the incidence of acquired T790M mutation in patients who had been treated with different types of EGFR TKIs. Patients harboring tumor with de novo T790M mutations were excluded.

Results

There were 410 patients who received re-biopsy for detection EGFR T790M after treating with 1^st- or 2^nd- generation EGFR TKIs. The overall acquired T790M mutation rate was 52.9%. Patients treated with gefitinib (59.8%) had higher acquired T790M incidence than those treated with erlotinib (45.5%; p = 0.011), but no difference with those treated with afatinib (53.3%; p = 0.236). Patients who had longer time to treatment discontinuation (TTD) of EGFR TKI for more than 18 months had higher T790M incidence than those with other predefined duration categories (p < 0.001). Multivariate logistic regression analysis revealed common EGFR mutations, gefitinib (compared to erlotinib), and longer TTD of EGFR TKI were associated with higher T790M incidence.

Conclusions

Patients treated with gefitinib had higher acquired T790M incidence than those treated with erlotinib. Longer TTD of EGFR TKI was also associated with the frequency of acquired T790M mutation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

AstraZeneca.

Disclosure

S-G. Wu: Honoraria (self): Roche; Honoraria (self): AstraZeneca. C-L. Chiang: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Roche. J-Y. Shih: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Novartis; Honoraria (self): Eli Lilly. G-C. Chang: Honoraria (self): F. Hoffmann-La Roche, Ltd; Honoraria (self): AstraZeneca; Honoraria (self): Eli Lilly and Company Oncology; Honoraria (self): Pfizer; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Merck Sharp & Dohme; Honoraria (self): Boehringer Ingelheim. All other authors have declared no conflicts of interest.