Clinical significance of monitoring EGFR mutation in plasma using multiplexed digital PCR in EGFR mutated patients treated with afatinib (West Japan Oncology Group 8114LTR study)

Hiroaki Akamatsu, Yasuhiro Koh, Isamu Okamoto, Daichi Fujimoto, Akihiro Bessho, Koichi Azuma, Satoshi Morita, Nobuyuki Yamamoto, Kazuhiko Nakagawa

Research output: Contribution to journalArticle

Abstract

Background: Liquid biopsy has been approved as an optional method to detect epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC). However, the clinical significance of its utility for monitoring the disease remains elusive. WJOG8114LTR is a prospective, multi-institutional study of liquid biopsy in EGFR mutated patients with NSCLC. Patients and methods: Chemotherapy naïve, advanced NSCLC patients with EGFR -sensitizing mutation received afatinib 40 mg/body until progressive disease (PD). Plasma DNA was obtained from patients at baseline, weeks 2, 4, 8, 12, 24, 48, and at PD. Three types of clinically relevant EGFR mutations (exon 19 deletion, exon 20 T790 M and exon 21 L858R) will be analyzed using plasma DNA with multiplexed, digital PCR assay. This study was registered at UMIN 000015847. Results: Fifty-seven patients were registered in the study. At baseline, 62.5% of patients were positive for EGFR mutation in plasma, and systemic spread of the tumor seemed to correlate with higher detection rate. After treatment, negative conversion of sensitive mutation within four weeks was observed among 87.5% of the patients. These patients demonstrated statistically significant longer progression-free survival than those who did not achieve negative conversion (13.6 months versus 5.1 months, p < 0.0001). Regarding progression, 35.7% of the patients showed recurrence in plasma DNA earlier than radiological progression. However, PFS curve based on plasma recurrence did not show significant difference than that based on RECIST. Conclusion: To predict durable efficacy and progression, liquid biopsy was useful in a part of EGFR mutated NSCLC patients.

Original languageEnglish
Pages (from-to)128-133
Number of pages6
JournalLung Cancer
Volume131
DOIs
Publication statusPublished - May 1 2019

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Epidermal Growth Factor Receptor
Japan
Polymerase Chain Reaction
Mutation
Non-Small Cell Lung Carcinoma
Exons
Biopsy
DNA
BIBW 2992
Recurrence
Disease-Free Survival
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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Clinical significance of monitoring EGFR mutation in plasma using multiplexed digital PCR in EGFR mutated patients treated with afatinib (West Japan Oncology Group 8114LTR study). / Akamatsu, Hiroaki; Koh, Yasuhiro; Okamoto, Isamu; Fujimoto, Daichi; Bessho, Akihiro; Azuma, Koichi; Morita, Satoshi; Yamamoto, Nobuyuki; Nakagawa, Kazuhiko.

In: Lung Cancer, Vol. 131, 01.05.2019, p. 128-133.

Research output: Contribution to journalArticle

Akamatsu, Hiroaki ; Koh, Yasuhiro ; Okamoto, Isamu ; Fujimoto, Daichi ; Bessho, Akihiro ; Azuma, Koichi ; Morita, Satoshi ; Yamamoto, Nobuyuki ; Nakagawa, Kazuhiko. / Clinical significance of monitoring EGFR mutation in plasma using multiplexed digital PCR in EGFR mutated patients treated with afatinib (West Japan Oncology Group 8114LTR study). In: Lung Cancer. 2019 ; Vol. 131. pp. 128-133.
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abstract = "Background: Liquid biopsy has been approved as an optional method to detect epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC). However, the clinical significance of its utility for monitoring the disease remains elusive. WJOG8114LTR is a prospective, multi-institutional study of liquid biopsy in EGFR mutated patients with NSCLC. Patients and methods: Chemotherapy na{\"i}ve, advanced NSCLC patients with EGFR -sensitizing mutation received afatinib 40 mg/body until progressive disease (PD). Plasma DNA was obtained from patients at baseline, weeks 2, 4, 8, 12, 24, 48, and at PD. Three types of clinically relevant EGFR mutations (exon 19 deletion, exon 20 T790 M and exon 21 L858R) will be analyzed using plasma DNA with multiplexed, digital PCR assay. This study was registered at UMIN 000015847. Results: Fifty-seven patients were registered in the study. At baseline, 62.5{\%} of patients were positive for EGFR mutation in plasma, and systemic spread of the tumor seemed to correlate with higher detection rate. After treatment, negative conversion of sensitive mutation within four weeks was observed among 87.5{\%} of the patients. These patients demonstrated statistically significant longer progression-free survival than those who did not achieve negative conversion (13.6 months versus 5.1 months, p < 0.0001). Regarding progression, 35.7{\%} of the patients showed recurrence in plasma DNA earlier than radiological progression. However, PFS curve based on plasma recurrence did not show significant difference than that based on RECIST. Conclusion: To predict durable efficacy and progression, liquid biopsy was useful in a part of EGFR mutated NSCLC patients.",
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AU - Akamatsu, Hiroaki

AU - Koh, Yasuhiro

AU - Okamoto, Isamu

AU - Fujimoto, Daichi

AU - Bessho, Akihiro

AU - Azuma, Koichi

AU - Morita, Satoshi

AU - Yamamoto, Nobuyuki

AU - Nakagawa, Kazuhiko

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Background: Liquid biopsy has been approved as an optional method to detect epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC). However, the clinical significance of its utility for monitoring the disease remains elusive. WJOG8114LTR is a prospective, multi-institutional study of liquid biopsy in EGFR mutated patients with NSCLC. Patients and methods: Chemotherapy naïve, advanced NSCLC patients with EGFR -sensitizing mutation received afatinib 40 mg/body until progressive disease (PD). Plasma DNA was obtained from patients at baseline, weeks 2, 4, 8, 12, 24, 48, and at PD. Three types of clinically relevant EGFR mutations (exon 19 deletion, exon 20 T790 M and exon 21 L858R) will be analyzed using plasma DNA with multiplexed, digital PCR assay. This study was registered at UMIN 000015847. Results: Fifty-seven patients were registered in the study. At baseline, 62.5% of patients were positive for EGFR mutation in plasma, and systemic spread of the tumor seemed to correlate with higher detection rate. After treatment, negative conversion of sensitive mutation within four weeks was observed among 87.5% of the patients. These patients demonstrated statistically significant longer progression-free survival than those who did not achieve negative conversion (13.6 months versus 5.1 months, p < 0.0001). Regarding progression, 35.7% of the patients showed recurrence in plasma DNA earlier than radiological progression. However, PFS curve based on plasma recurrence did not show significant difference than that based on RECIST. Conclusion: To predict durable efficacy and progression, liquid biopsy was useful in a part of EGFR mutated NSCLC patients.

AB - Background: Liquid biopsy has been approved as an optional method to detect epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC). However, the clinical significance of its utility for monitoring the disease remains elusive. WJOG8114LTR is a prospective, multi-institutional study of liquid biopsy in EGFR mutated patients with NSCLC. Patients and methods: Chemotherapy naïve, advanced NSCLC patients with EGFR -sensitizing mutation received afatinib 40 mg/body until progressive disease (PD). Plasma DNA was obtained from patients at baseline, weeks 2, 4, 8, 12, 24, 48, and at PD. Three types of clinically relevant EGFR mutations (exon 19 deletion, exon 20 T790 M and exon 21 L858R) will be analyzed using plasma DNA with multiplexed, digital PCR assay. This study was registered at UMIN 000015847. Results: Fifty-seven patients were registered in the study. At baseline, 62.5% of patients were positive for EGFR mutation in plasma, and systemic spread of the tumor seemed to correlate with higher detection rate. After treatment, negative conversion of sensitive mutation within four weeks was observed among 87.5% of the patients. These patients demonstrated statistically significant longer progression-free survival than those who did not achieve negative conversion (13.6 months versus 5.1 months, p < 0.0001). Regarding progression, 35.7% of the patients showed recurrence in plasma DNA earlier than radiological progression. However, PFS curve based on plasma recurrence did not show significant difference than that based on RECIST. Conclusion: To predict durable efficacy and progression, liquid biopsy was useful in a part of EGFR mutated NSCLC patients.

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