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Poster display

1530 - Analysis of circulating cell-free DNA in plasma shows a higher detection rate of EGFR mutations in patients with extrathoracic disease progression

Date

10 Oct 2016

Session

Poster display

Presenters

Yoshitaka Seki

Citation

Annals of Oncology (2016) 27 (6): 545-551. 10.1093/annonc/mdw393

Authors

Y. Seki1, Y. Fujiwara2, T. Kohno1, Y. Goto2, H. Horinouchi2, S. Kanda2, H. Nokihara2, N. Yamamoto2, K. Kuwano3, Y. Ohe2

Author affiliations

  • 1 Division Of Genome Biology, National Cancer Center Research Institute, 104-0045 - Tokyo/JP
  • 2 Department Of Thoracic Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 3 Division Of Respirology, Department Of Internal Medicine, Jikei University School of Medicine, 105-8471 - Tokyo/JP
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Abstract 1530

Background

Noninvasive monitoring of EGFR mutations conferring sensitivity (i.e., L858R and various types of exon 19 deletion mutations) and resistance (i.e., T790M and C797S) to tyrosine kinase inhibitors (TKIs) is vital for efficient therapy of lung adenocarcinoma (LADC) with conventional and/or new generation EGFR-TKIs. Although plasma cell-free DNA (cfDNA) is detectable at an early stage, the size of the tumors does not significantly correlate with cfDNA concentration. We explored clinical features of patients with LADC whose cfDNA examination was useful.

Methods

Forty-four plasma samples from 37 LADC patients receiving EGFR-TKI therapy, including 20 who developed resistance, were prospectively subjected to droplet digital PCR-cfDNA analysis to determine the fraction of cfDNA with EGFR mutations, and analyzed according to clinical features. The factors subjected to analysis were age, sex, ECOG PS, sites of metastatic disease, and sites of recent progressive disease.

Results

cfDNA samples from 19 (95%) of the 20 resistant patients were positive for TKI-sensitive mutations as previously reported. Also, 26 (84%) of 31 patients with extrathoracic disease progression, and 24 (86%) of 28 with regional lymph node metastases, were similarly positive. cfDNA analysis from patients with these features correlated with a high detection rate of TKI-sensitive mutations (acquired resistance: risk ratio: 2.073, 95% CI: 1.326-3.239; extrathoracic disease progression: risk ratio: 2.726, 95% CI: 1.189-6.250; lymph node metastases: risk ratio: 2.095, 95% CI: 1.052-4.174). Presence and cites of metastatic diseases were not correlated with detection rate significantly.

Conclusions

EGFR mutation detection from cfDNA is useful in EGFR-TKI-resistant patients, especially those with extrapleural disease progression. One possible explanation for this difference is that migration potency of tumor cells might increase the amount of plasma cfDNA by promoting the dissemination of tumor cells into plasma. Further analysis of cfDNA from patients with these features may be useful for tumor molecular profiling and treatment modification.

Clinical trial identification

The study was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN 000017581).

Legal entity responsible for the study

Yutaka Fujiwara

Funding

The Ministry of Health Labour and Welfare, Japan

Disclosure

Y. Goto: Eli Lilly, Boehringer Ingelheim (Consulting, Honoraria received), AstraZeneca (Honoraria received). H. Horinouchi: Corporate-sponsored research: Taiho, Merck Serono, MSD, Astellas, Novartis. H. Nokihara: Merck Serono, Pfizer, Eisai, Chugai Pharma, Novartis, Daiichi Sankyo, GlaxoSmithKline, Yakult, Quintiles, Astellas, (Research funding), Sanofi (Honoraria received), Taiho, Eli Lilly, Boehringer Ingelheim, AstraZeneca, Ono (Honoraria & funding). N. Yamamoto: Quintiles, Astellas, Chugai, Esai, Taiho, BMS, Pfizer, Novartis, Daiichi-Sankyo, Boehringer Ingelheim, Kyowa-Hakko Kirin (Research funding), AstraZeneca, Pfizer, Eli Lilly, Chugai(Honoraria received). Y. Ohe: AstraZeneca, Chugai, Taiho Pharmaceutical, Ono, Bristol-Myers Squibb,(Research funding)(Honoraria received) Sumitomo Dainippon, Kyorin,(Research funding;) Lilly, Pfizer, Boehringer Ingelheim, (Honoraria received). All other authors have declared no conflicts of interest.

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