Cancer Res Treat.  2022 Oct;54(4):985-995. 10.4143/crt.2021.857.

Assessment of Anti-tumor Efficacy of Osimertinib in Non-Small Cell Lung Cancer Patients by Liquid Biopsy Using Bronchoalveolar Lavage Fluid, Plasma, or Pleural Effusion

• Kim YJ
• Ji WJ
• Lee JC
• Chun SM
• Choi CM

• KMID: 2534178
• DOI: http://doi.org/10.4143/crt.2021.857

Abstract

Purpose
This study was to evaluate anti-tumor efficacy of osimertinib in patients positive for acquired epidermal growth factor receptor (EGFR) T790M mutation in liquid biopsy using plasma, bronchoalveolar lavage fluid (BALF) or bronchial washing fluid (BWF), and pleural effusion.
Materials and Methods
Among patients benefited from previous EGFR‒tyrosine kinase inhibitor treatment followed by treatment failure, patients in whom T790M mutations are detected in at least one of the samples including tumor tissues, BALF/BWF, plasma, and pleural effusion were enrolled. T790M mutation was detected by extracting cell free DNA from liquid biopsy samples, using PANA Mutyper. Objective response rate (ORR) and progression-free survival (PFS) with osimertinib treatment were evaluated.
Results
Between January 2018 and December 2019, 63 patients were enrolled and received osimertinib. Mean age was 63 years, and 38 (60.3%) were female. Twenty-six patients had T790M mutation in both liquid and tissue samples (group A), 19 patients had only in tissue biopsy samples (group B), and 18 patients had T790M mutation only in liquid biopsy samples (group C). ORR in overall population was 63.5%, and was 61.5% in group A, 68.4% in group B, and 61.1% in group C, respectively. Median PFS in overall patients was 15.6 months (95% confidence interval, 10.7 to 24.2). There was no significant difference in ORR or PFS between groups.
Conclusion
Osimertinib showed favorable efficacy in lung cancer patients with acquired resistance to prior EGFR-TKI therapies, who screened positive for harboring T790M mutation detected from cell free DNA extracted from plasma, BALF/BWF, and pleural effusion.

Keyword

Non-small cell lung carcinoma; Osimertinib; T790M; Liquid biopsies

Figure

• 

  Fig. 1 Patient flowchart. One hundred twenty-four patients who previously benefited from EGFR-TKI treatment and eventually experienced disease progression were enrolled. From 78 T790M detected in either tissue or liquid biopsy specimens, 63 patients were enrolled and received osimertinib. BALF, bronchoalveolar lavage fluid; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; NSCLC, non–small cell lung cancer; T790M, (c.2369C>T; p.Thr790Met); TKI, tyrosine kinase inhibitor.

• 

  Fig. 2 Grouping of the subjects according to T790M mutation status in tissue or liquid biopsy samples. T790M positivity by the type of biopsy sample in overall population are shown as a diagram. Group A, patients who have T790M mutation detected in both tissue and liquid biopsy samples; Group B, patients who have T790M mutation detected only in tissue; Group C, patients who have T790M mutation detected only in liquid biopsy samples. BALF, bronchoalveolar lavage fluid; PE, pleural effusion; T790M, (c.2369C>T; p.Thr790Met).

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  Fig. 3 Objective response rates by T790M positivity status in tissue or liquid biopsy samples. Objective response rates according to Response Evaluation Criteria in Solid Tumors in the response evaluable population are shown by T790M positivity in tissue or liquid biopsy samples. Group A, patients who have T790M mutation detected in both tissue and liquid biopsy samples; Group B, patients who have T790M mutation detected only in tissue; Group C, patients who have T790M mutation detected only in liquid biopsy samples. CR, complete response; PD, progression of disease; PR, partial response; SD, stable disease; T790M, (c.2369C>T; p.Thr790Met).

• 

  Fig. 4 Tumor response to osimertinib by T790M positivity status in tissue or liquid biopsy samples. Waterfall plot according to Response Evaluation Criteria in Solid Tumors in the response evaluable population are shown by T790M positivity in tissue or liquid biopsy samples. (A) Overall patients (n=63). (B) Group A (n=26): patients who have T790M mutation detected in both tissue and liquid biopsy samples. (C) Group B (n=19): patients who have T790M mutation detected only in tissue. (D) Group C (n=18): patients who have T790M mutation detected only in liquid biopsy samples. PD (blue bar), progression of disease; PR (red bar), partial response; SD (green bar), stable disease; T790M, (c.2369C>T; p.Thr790Met).

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  Fig. 5 Progression-free survival after osimertinib treatment. Progression-free survival after treatment with osimertinib in overall patients (n=63) (A) and by T790M positivity (B) in tissue or liquid biopsy samples are shown. Group A (n=26), patients who have T790M mutation detected in both tissue and liquid biopsy samples; Group B (n=19), patients who have T790M mutation detected only in tissue; Group C (n=18), patients who have T790M mutation detected only in liquid biopsy samples; T790M, (c.2369C>T; p.Thr790Met).

Reference

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