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. 2024 Jan 19:16:17588359231222604.
doi: 10.1177/17588359231222604. eCollection 2024.

Differential prognostic value of tumor and plasma T790M mutations in EGFR TKI-treated advanced NSCLC

Pi-Hung Tung  1   2 , Tzu-Hsuan Chiu  1   2 , Allen Chung-Cheng Huang  1   2 , Jia-Shiuan Ju  1   2 , Chi-Hsien Huang  1   2 , Chin-Chou Wang  3 , How-Wen Ko  1   2 , Fu-Tsai Chung  1   2 , Ping-Chih Hsu  1   2 , Yueh-Fu Fang  1   2 , Yi-Ke Guo  4 , Chih-Hsi Scott Kuo  5   6   4 , Cheng-Ta Yang  1   2
Affiliations

Differential prognostic value of tumor and plasma T790M mutations in EGFR TKI-treated advanced NSCLC

Pi-Hung Tung et al. Ther Adv Med Oncol. .

Abstract

Background: Substitution of methionine for threonine at codon 790 (T790M) of epidermal growth factor receptor (EGFR) represents the major mechanism of resistance to EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small-cell lung cancer. We determined the prognostic impact and association of secondary T790M mutations with the outcomes of osimertinib and chemotherapy.

Methods: Patients (n = 460) progressing from first-line EGFR-TKI treatment were assessed. Tissue and/or liquid biopsies were used to determine T790M status; post-progression overall survival (OS) was analyzed.

Results: Overall, 143 (31.1%) patients were T790M positive, 95 (20.7%) were T790M negative, and 222 (48.2%) had unknown T790M status. T790M status [T790M positive versus T790M negative: hazard ratio (HR) 0.48 (95% confidence interval (CI), 0.32-0.70); p < 0.001, T790M unknown versus T790M negative: HR 1.97 (95% CI, 1.47-2.64); p < 0.001] was significantly associated with post-progression OS. T790M positivity rates were similar for tissue (90/168, 53.6%) and liquid (53/90, 58.9%) biopsies (Fisher's exact test, p = 0.433). Tumor T790M-positive patients had significantly longer post-progression OS than tumor T790M-negative patients (34.1 versus 17.1 months; log-rank test, p = 8 × 10-5). Post-progression OS was similar between plasma T790M-positive and -negative patients (17.4 versus not reached; log-rank test, p = 0.600). In tumor T790M-positive patients, post-progression OS was similar after osimertinib and chemotherapy [34.1 versus 29.1 months; log-rank test, p = 0.900; HR 1.06 (95% CI, 0.44-2.57); p = 0.897].

Conclusion: T790M positivity predicts better post-progression OS than T790M negativity; tumor T790M positivity has a stronger prognostic impact than plasma T790M positivity. Osimertinib and chemotherapy provide similar OS benefits in patients with T790M-positive tumors.

Keywords: EGFR; chemotherapy; osimertinib; plasma T790M; tumor T790M.

Plain language summary

Different prognostic meaning of tumor resistant gene detected from tumor or blood in patients with EGFR-mutant lung cancer The study demonstrates that patients with EGFR-mutant lung cancer who develop resistance due to a secondary T790M mutation, defined by tumor or blood T790M positivity, achieve better survival than patients without secondary T790M mutation; this association was mainly contributed by tumour T790M positivity. Oismertinib and chemotherapy led to similar survival in tumour T790M-positive patients. However, compared to osimertinib, chemotherapy was associated with longer survival in blood T790M-positive patients.

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Conflict of interest statement

C-HSK received speaker honoraria from AstraZeneca, Boehringer Ingelheim, Roche, Pfizer, Eli Lilliy, Novartis, OnO Pharma, Chugai, Merck, Janssen Pharma, Takeda, and Guardant Health. C-HSK provided consultation for AstraZeneca, Boehringer Ingelheim, Eli Lilliy, Merck, Chugai, Takeda, Novartis, and Guardant Health. None of the other authors have any conflict of interest to disclose.

Figures

Figure 1.
Figure 1.
Post-progression OS for T790M-positive patients (blue), T790M-negative patients (red), and patients with unknown T790M status (green). OS, overall survival.
Figure 2.
Figure 2.
Post-progression OS for (a) tumor T790M-positive and -negative patients and (b) plasma T790M-positive and -negative patients. OS, overall survival.
Figure 3.
Figure 3.
Post-progression OS for osimertinib treatment and chemotherapy in (a) tumor T790M-positive patients and (b) tumor T790M-negative patients. OS, overall survival.
Figure 4.
Figure 4.
Post-progression OS for osimertinib treatment and chemotherapy in (a) plasma T790M-positive patients and (b) plasma T790M-negative patients. OS, overall survival.
See this image and copyright information in PMC

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