Hiroaki Akamatsu1, Yasuhiro Koh1, Isamu Okamoto2, Daichi Fujimoto3, Akihiro Bessho4, Koichi Azuma5, Satoshi Morita6, Nobuyuki Yamamoto7, Kazuhiko Nakagawa8. 1. Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan. 2. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 3. Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan. 4. Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital, Okayama, Japan. 5. Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan. 6. Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine Kyoto, Japan. 7. Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan. Electronic address: nbyamamo@wakayama-med.ac.jp. 8. Department of Medical Oncology, Faculty of Medicine, Kindai University, Osaka, Japan.
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.
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 NSCLCpatients 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 NSCLCpatients.
Authors: Frederik van Delft; Hendrik Koffijberg; Valesca Retèl; Michel van den Heuvel; Maarten IJzerman Journal: Cancers (Basel) Date: 2020-04-30 Impact factor: 6.639