Abstract 5204: Exploring the therapeutic potential of EGFR retreatment: A comprehensive analysis of T790m(+) conversion and prognosis in lung cancer patients

Abstract Background: T790M acquired resistance occurs in 30-40% of cases after first- or second-generation EGFR TKI treatment. However, some patients who did not develop T790M mutation are converted to T790M positive through EGFR TKI retreatment. We conducted a Phase II prospective study analyzing T790m (+) conversion and prognosis in patients who were not induced T790M mutation at 2nd biopsy and were re-treated with first-generation EGFR-TKI as the third-line or later therapy. Methods: We re-administered first-generation EGFR-TKI to 63 patients (gefitinib n=34 or erlotinib n=29) who had previously been treated with first- or second- generation EGFR TKIs and cytotoxic chemotherapy because they were T790M-negative at the 2nd biopsy. Results: Among the 63 patients, a new T790m (+) mutation was identified in 20 patients (32%) with EGFR TKI retreatment. The first EGFR TKI treatment period and EGFR TKI retreatment period were significantly longer in the T790m (+) group than in the T790m (-) group (P-value=0.026, P-value=0.029, respectively). The best response to retreatment was also favorable in the T790m (+) group (P-value=0.038). The median overall survival (OS) in the T790m (+) group was 29.3 months, which was significantly better than the 6.0 months observed in the T790m (-) group (P-value<0.001). In an additional NGS analysis conducted on stored plasma samples from the 24 patients who were negative for T790M in the tumor tissue before retreatment, T790M was detected in five patients. These patients, who were subsequently treated with a third EGFR TKI, demonstrated very favorable overall survival (OS). Conclusions: EGFR retreatment could induce T790m (+) conversion in approximately one-third of cases, and these patients exhibited favorable prognosis. Through NGS analysis using plasma samples, approximately 20% cases of T790m mutation, which were not detected through routine PCR tests at the tumor tissue, could be identified. Retreatment-EGFR TKI and NGS analysis through blood samples could improve patient prognosis through the additional discovery of T790m (+) mutation. Citation Format: Joong Jin Ahn, Jae Cheol Lee, Chang Min Choi, In Ae Kim, Kye Young Lee, Jeong Eun Lee, Seung Hoon Jang, Seong Hoon Yoon, In Jae Oh, Sang Hoon Lee, Eun Young Kim, Juwhan Choi, Sung Yong Lee. Exploring the therapeutic potential of EGFR retreatment: A comprehensive analysis of T790m(+) conversion and prognosis in lung cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5204.