A Retrospective Analysis of the Factors Affecting the Detection of T790M-resistant Mutation on Rebiopsies for Patients with Non-small-cell Lung Cancer Harboring EGFR Mutations
Background/Objective. Osimertinib is generally used as a second-line or later therapy after the detection of a T790M mutation by a rebiopsy in non-small-cell lung cancer (NSCLC). However, few reports have described the results of rebiopsies in NSCLC patients with EGFR mutations. The aim of our retro...
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| Published in | The Journal of the Japan Society for Respiratory Endoscopy Vol. 42; no. 1; pp. 6 - 13 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
The Japan Society for Respiratory Endoscopy
25.01.2020
特定非営利活動法人 日本呼吸器内視鏡学会 |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0287-2137 2186-0149 |
| DOI | 10.18907/jjsre.42.1_6 |
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| Abstract | Background/Objective. Osimertinib is generally used as a second-line or later therapy after the detection of a T790M mutation by a rebiopsy in non-small-cell lung cancer (NSCLC). However, few reports have described the results of rebiopsies in NSCLC patients with EGFR mutations. The aim of our retrospective study was to identify factors affecting the detection of a T790M mutation in patients who undergo a rebiopsy. Method. This study included subjects who had advanced NSCLC with EGFR mutations and underwent rebiopsies at our hospital from January 2016 to April 2018. We investigated the success rate of rebiopsies, the detection rate of T790M, and the influential factors related to rebiopsies and T790M detection. Result. The subjects were 58 patients who underwent a rebiopsy. The success rate of the first rebiopsy was 74.1% (43/58), and the T790M-positive rate was 41.9% (18/43). The success rate of the second rebiopsy was 78.6% (11/14), and the T790M-positive rate was 63.6% (7/11). The overall number of rebiopsies was 75, the overall success rate of rebiopsies was 76.0% (57/75), and the overall T790M-positive rate was 43.9% (25/57). No statistically significant factors affecting the T790M-positive rate were observed in this study. In addition, the characteristics of patients who underwent multiple rebiopsies as well as the characteristics of those who only underwent a single rebiopsy were examined. The frequency of experiencing multiple rebiopsies was higher in patients with cytotoxic agents than in those without (P=0.005). Conclusion. We were unable to detect any factors affecting positivity for a T790M mutation. The frequency of having undergone several rebiopsies seemed to be higher in patients who received any cytotoxic chemotherapy than in those with no such treatment. We believe that repeated specimen collection may increase the detection rate for T790M mutations. |
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| AbstractList | Background/Objective. Osimertinib is generally used as a second-line or later therapy after the detection of a T790M mutation by a rebiopsy in non-small-cell lung cancer (NSCLC). However, few reports have described the results of rebiopsies in NSCLC patients with EGFR mutations. The aim of our retrospective study was to identify factors affecting the detection of a T790M mutation in patients who undergo a rebiopsy. Method. This study included subjects who had advanced NSCLC with EGFR mutations and underwent rebiopsies at our hospital from January 2016 to April 2018. We investigated the success rate of rebiopsies, the detection rate of T790M, and the influential factors related to rebiopsies and T790M detection. Result. The subjects were 58 patients who underwent a rebiopsy. The success rate of the first rebiopsy was 74.1% (43/58), and the T790M-positive rate was 41.9% (18/43). The success rate of the second rebiopsy was 78.6% (11/14), and the T790M-positive rate was 63.6% (7/11). The overall number of rebiopsies was 75, the overall success rate of rebiopsies was 76.0% (57/75), and the overall T790M-positive rate was 43.9% (25/57). No statistically significant factors affecting the T790M-positive rate were observed in this study. In addition, the characteristics of patients who underwent multiple rebiopsies as well as the characteristics of those who only underwent a single rebiopsy were examined. The frequency of experiencing multiple rebiopsies was higher in patients with cytotoxic agents than in those without (P=0.005). Conclusion. We were unable to detect any factors affecting positivity for a T790M mutation. The frequency of having undergone several rebiopsies seemed to be higher in patients who received any cytotoxic chemotherapy than in those with no such treatment. We believe that repeated specimen collection may increase the detection rate for T790M mutations.
背景・目的．Osimertinibを2次治療以降で使用する場合，再生検でT790M耐性変異を検出する必要がある．しかし，再生検についての報告は少ない．今回，再生検の現状，T790M耐性変異検出に影響を与える因子をretrospectiveに評価した．方法．2016年1月から2018年4月の間，当院で再生検が行われたEGFR遺伝子変異陽性非小細胞肺癌を抽出し，再生検成功率とT790M陽性率，T790M耐性変異が検出された患者と複数回の生検施行患者の背景を調査し，影響を与える因子を検討した．結果．再生検が行われた58人を対象とした．1度目の再生検成功率は74.1%（43/58人），T790M陽性率41.9%（18/43人）であった．2度目の再生検成功率は78.6%（11/14人），T790M陽性率63.6%（7/11人）となった．全再生検施行回数は75回，全再生検成功率76.0%（57/75回），全T790M陽性率43.9%（25/57回）であった．T790M陽性率に関係がある要因を検討した．検討した項目に関して，有意差が認められるものは存在しなかった．再生検を複数回施行した患者と再生検施行が1度のみの患者を比較したところ，細胞障害性抗癌薬治療を行った患者の方が複数回の再生検を施行している傾向にあった（P=0.005）．結論．T790M耐性変異検出に影響を与える因子は認められなかった．細胞障害性抗癌薬治療歴がある方が，複数回の再生検を行う傾向にあり，繰り返しの検体採取によりT790M耐性変異の検出率が増加する可能性が考えられた． Background/Objective. Osimertinib is generally used as a second-line or later therapy after the detection of a T790M mutation by a rebiopsy in non-small-cell lung cancer (NSCLC). However, few reports have described the results of rebiopsies in NSCLC patients with EGFR mutations. The aim of our retrospective study was to identify factors affecting the detection of a T790M mutation in patients who undergo a rebiopsy. Method. This study included subjects who had advanced NSCLC with EGFR mutations and underwent rebiopsies at our hospital from January 2016 to April 2018. We investigated the success rate of rebiopsies, the detection rate of T790M, and the influential factors related to rebiopsies and T790M detection. Result. The subjects were 58 patients who underwent a rebiopsy. The success rate of the first rebiopsy was 74.1% (43/58), and the T790M-positive rate was 41.9% (18/43). The success rate of the second rebiopsy was 78.6% (11/14), and the T790M-positive rate was 63.6% (7/11). The overall number of rebiopsies was 75, the overall success rate of rebiopsies was 76.0% (57/75), and the overall T790M-positive rate was 43.9% (25/57). No statistically significant factors affecting the T790M-positive rate were observed in this study. In addition, the characteristics of patients who underwent multiple rebiopsies as well as the characteristics of those who only underwent a single rebiopsy were examined. The frequency of experiencing multiple rebiopsies was higher in patients with cytotoxic agents than in those without (P=0.005). Conclusion. We were unable to detect any factors affecting positivity for a T790M mutation. The frequency of having undergone several rebiopsies seemed to be higher in patients who received any cytotoxic chemotherapy than in those with no such treatment. We believe that repeated specimen collection may increase the detection rate for T790M mutations. |
| Author | Kaira, Kyouichi Kagamu, Hiroshi Kobayashi, Kunihiko Shiono, Ayako Mouri, Atsuto Yamaguchi, Ou Miura, Yu Uchida, Takahiro Nishihara, Fuyumi Hashimoto, Kousuke |
| Author_FL | Shiono Ayako 山口 央 三浦 雄 小林 国彦 橋本 康佑 各務 博 西原 冬実 解良 恭一 Mouri Atsuto 内田 貴裕 |
| Author_FL_xml | – sequence: 1 fullname: 内田 貴裕 – sequence: 2 fullname: Mouri Atsuto – sequence: 3 fullname: 橋本 康佑 – sequence: 4 fullname: 三浦 雄 – sequence: 5 fullname: Shiono Ayako – sequence: 6 fullname: 西原 冬実 – sequence: 7 fullname: 山口 央 – sequence: 8 fullname: 解良 恭一 – sequence: 9 fullname: 各務 博 – sequence: 10 fullname: 小林 国彦 |
| Author_xml | – sequence: 1 fullname: Mouri, Atsuto organization: Department of Respiratory Medicine, Saitama Medical University International Medical Center – sequence: 1 fullname: Miura, Yu organization: Department of Respiratory Medicine, Saitama Medical University International Medical Center – sequence: 1 fullname: Hashimoto, Kousuke organization: Department of Respiratory Medicine, Saitama Medical University International Medical Center – sequence: 1 fullname: Shiono, Ayako organization: Department of Respiratory Medicine, Saitama Medical University International Medical Center – sequence: 1 fullname: Kobayashi, Kunihiko organization: Department of Respiratory Medicine, Saitama Medical University International Medical Center – sequence: 1 fullname: Uchida, Takahiro organization: Department of Respiratory Medicine, Saitama Medical University Hospital – sequence: 1 fullname: Kaira, Kyouichi organization: Department of Respiratory Medicine, Saitama Medical University International Medical Center – sequence: 1 fullname: Nishihara, Fuyumi organization: Department of Respiratory Medicine, Saitama Medical University International Medical Center – sequence: 1 fullname: Yamaguchi, Ou organization: Department of Respiratory Medicine, Saitama Medical University International Medical Center – sequence: 1 fullname: Kagamu, Hiroshi organization: Department of Respiratory Medicine, Saitama Medical University International Medical Center |
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| DocumentTitle_FL | EGFR遺伝子変異陽性非小細胞肺癌の再生検においてT790M耐性変異検出に影響を与える因子の検討 |
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| References_xml | – reference: 4. Seike M, Inoue A, Sugawara S, et al. Phase III study of gefitinib (G) versus gefitinib＋carboplatin＋pemetrexed (GCP) as first-line treatment for patients (pts) with advanced non-small cell lung cancer (NSCLC) with EGFR mutations (NEJ009). Ann Oncol. 2018;29 (Suppl 8):viii493-viii547. – reference: 1. Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378:113-125. – reference: 2. Ramalingam SS, Yang JC, Lee CK, et al. Osimertinib as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer. J Clin Oncol. 2018;36:841-849. – reference: 8. Izumo T, Matsumoto Y, Chavez C, et al. Re-biopsy by endobronchial ultrasound procedures for mutation analysis of non-small cell lung cancer after EGFR tyrosine kinase inhibitor treatment. BMC Pulm Med. 2016;16:106. – reference: 10. Tseng JS, Su KY, Yang TY, et al. The emergence of T790M mutation in EGFR-mutant lung adenocarcinoma patients having a history of acquired resistance to EGFR-TKI: focus on rebiopsy timing and long-term existence of T790M. Oncotarget. 2016;7:48059-48069. – reference: 3. Nakamura A, Inoue A, Morita S, et al. Phase III study comparing gefitinib monotherapy (G) to combination therapy with gefitinib, carboplatin, and pemetrexed (GCP) for untreated patients (pts) with advanced non-small cell lung cancer (NSCLC) with EGFR mutations (NEJ009). J Clin Oncol. 2018;36 (Suppl):9005. – reference: 12. Hata A, Katakami N, Yoshioka H, et al. Spatiotemporal T790M heterogeneity in individual patients with EGFR-mutant non-small-cell lung cancer after acquired resistance to EGFR-TKI. J Thorac Oncol. 2015;10:1553-1559. – reference: 5. Seto T, Nogami N, Yamamoto N, et al. Real-world EGFR T790M testing in advanced non-small-cell lung cancer: a prospective observational study in japan. Oncol Ther. 2018;6:203-215. – reference: 11. Oya Y, Yoshida T, Kuroda H, et al. Association between EGFR T790M status and progression patterns during initial EGFR-TKI treatment in patients harboring EGFR mutation. Clin Lung Cancer. 2017;18:698-705.e2. – reference: 13. Mok TS, Wu Y-L, Ahn M-J, et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017;376:629-640. – reference: 6. Nosaki K, Satouchi M, Kurata T, et al. Re-biopsy status among non-small cell lung cancer patients in Japan: a retrospective study. Lung Cancer. 2016;101:1-8. – reference: 9. Yoshida T, Tanaka H, Kuroda H, et al. Standardized uptake value on (18) F-FDG-PET/CT is a predictor of EGFR T790M mutation status in patients with acquired resistance to EGFR-TKIs. Lung Cancer. 2016;100:14-19. – reference: 7. Kawamura T, Kenmotsu H, Taira T, et al. Rebiopsy for patients with non-small-cell lung cancer after epidermal growth factor receptor-tyrosine kinase inhibitor failure. Cancer Sci. 2016;107:1001-1005. |
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| Title | A Retrospective Analysis of the Factors Affecting the Detection of T790M-resistant Mutation on Rebiopsies for Patients with Non-small-cell Lung Cancer Harboring EGFR Mutations |
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