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

Autor:	Tung PH; Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taipei, Taiwan.; Thoracic Oncology Unit, Chang Gung Memorial Hospital Cancer Center, Taipei, Taiwan., Chiu TH; Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taipei, Taiwan.; Thoracic Oncology Unit, Chang Gung Memorial Hospital Cancer Center, Taipei, Taiwan., Huang AC; Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taipei, Taiwan.; Thoracic Oncology Unit, Chang Gung Memorial Hospital Cancer Center, Taipei, Taiwan., Ju JS; Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taipei, Taiwan.; Thoracic Oncology Unit, Chang Gung Memorial Hospital Cancer Center, Taipei, Taiwan., Huang CH; Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taipei, Taiwan.; Thoracic Oncology Unit, Chang Gung Memorial Hospital Cancer Center, Taipei, Taiwan., Wang CC; Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan., Ko HW; Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taipei, Taiwan.; Thoracic Oncology Unit, Chang Gung Memorial Hospital Cancer Center, Taipei, Taiwan., Chung FT; Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taipei, Taiwan.; Thoracic Oncology Unit, Chang Gung Memorial Hospital Cancer Center, Taipei, Taiwan., Hsu PC; Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taipei, Taiwan.; Thoracic Oncology Unit, Chang Gung Memorial Hospital Cancer Center, Taipei, Taiwan., Fang YF; Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taipei, Taiwan.; Thoracic Oncology Unit, Chang Gung Memorial Hospital Cancer Center, Taipei, Taiwan., Guo YK; Data Science Institute, Department of Computing, Imperial College London, London, UK., Kuo CS; Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, No. 199, Tun-Hwa North Road, Taipei 333, Taiwan.; Thoracic Oncology Unit, Chang Gung Memorial Hospital Cancer Center.; Data Science Institute, Department of Computing, Imperial College London, London, UK., Yang CT; Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taipei, Taiwan.; Thoracic Oncology Unit, Chang Gung Memorial Hospital Cancer Center, Taipei, Taiwan.
Jazyk:	angličtina
Zdroj:	Therapeutic advances in medical oncology [Ther Adv Med Oncol] 2024 Jan 19; Vol. 16, pp. 17588359231222604. Date of Electronic Publication: 2024 Jan 19 (Print Publication: 2024).
DOI:	10.1177/17588359231222604
Abstrakt:	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. Competing Interests: 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. (© The Author(s), 2024.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu