甲状腺癌に対するゲノム医療
根治切除不能甲状腺がんに対してソラフェニブ，レンバチニブ，バンデタニブなどのマルチキナーゼ阻害薬が使用可能になったが，薬剤耐性になった場合の治療選択肢は限られる。現在，がんゲノム医療が甲状腺がんにも進展している。セルペルカチニブは，RET遺伝子異常を有する固形癌患者を対象としたバスケット試験にて，根治切除不能なRET遺伝子異常陽性の甲状腺がんに対して良好な抗腫瘍効果，奏効期間，PFSを示し，承認された。がん遺伝子パネル検査は，実施可能施設に制限があったが，セルペルカチニブのコンパニオン診断薬であるオンコマインDx Target TestマルチCDxシステムは，全医療機関で実施可能になった。これ...
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| Published in | 日本内分泌外科学会雑誌 Vol. 40; no. 1; pp. 33 - 37 |
|---|---|
| Main Author | |
| Format | Journal Article |
| Language | Japanese |
| Published |
一般社団法人 日本内分泌外科学会
2023
|
| Subjects | |
| Online Access | Get full text |
| ISSN | 2434-6535 2758-8785 |
| DOI | 10.11226/ojjaes.40.1_33 |
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| Abstract | 根治切除不能甲状腺がんに対してソラフェニブ，レンバチニブ，バンデタニブなどのマルチキナーゼ阻害薬が使用可能になったが，薬剤耐性になった場合の治療選択肢は限られる。現在，がんゲノム医療が甲状腺がんにも進展している。セルペルカチニブは，RET遺伝子異常を有する固形癌患者を対象としたバスケット試験にて，根治切除不能なRET遺伝子異常陽性の甲状腺がんに対して良好な抗腫瘍効果，奏効期間，PFSを示し，承認された。がん遺伝子パネル検査は，実施可能施設に制限があったが，セルペルカチニブのコンパニオン診断薬であるオンコマインDx Target TestマルチCDxシステムは，全医療機関で実施可能になった。これによって，甲状腺癌にもゲノム医療が推進することが期待される。しかし，頻度の高いBRAFV600E陽性患者に対する治療薬は未だ承認されておらず，がんゲノム難民が生じている。個別化医療を推進するためには，初回治療時の遺伝子異常検査が実施可能にすべきである。 |
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| AbstractList | 根治切除不能甲状腺がんに対してソラフェニブ，レンバチニブ，バンデタニブなどのマルチキナーゼ阻害薬が使用可能になったが，薬剤耐性になった場合の治療選択肢は限られる。現在，がんゲノム医療が甲状腺がんにも進展している。セルペルカチニブは，RET遺伝子異常を有する固形癌患者を対象としたバスケット試験にて，根治切除不能なRET遺伝子異常陽性の甲状腺がんに対して良好な抗腫瘍効果，奏効期間，PFSを示し，承認された。がん遺伝子パネル検査は，実施可能施設に制限があったが，セルペルカチニブのコンパニオン診断薬であるオンコマインDx Target TestマルチCDxシステムは，全医療機関で実施可能になった。これによって，甲状腺癌にもゲノム医療が推進することが期待される。しかし，頻度の高いBRAFV600E陽性患者に対する治療薬は未だ承認されておらず，がんゲノム難民が生じている。個別化医療を推進するためには，初回治療時の遺伝子異常検査が実施可能にすべきである。 |
| Author | 田原, 信 |
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Subbiah V, Cassier PA, Siena S, et al.: Pan-cancer efficacy of pralsetinib in patients with RET fusion-positive solid tumors from the phase 1/2 ARROW trial. Nature Medicine 28: 1640-1645, 2022 11. Waguespack SG, Drilon A, Lin JJ, et al.: Efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma. European Journal of Endocrinology 186: 631-643, 2022 25. Dummer R, Schadendorf D, Ascierto PA, et al.: Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 18: 435-445, 2017 14. Drilon A, Nagasubramanian R, Blake JF, et al.: A Next-Generation TRK Kinase Inhibitor Overcomes Acquired Resistance to Prior TRK Kinase Inhibition in Patients with TRK Fusion-Positive Solid Tumors. Cancer Discov 7: 963-972, 2017 24. Hong DS, Fakih MG, Strickler JH, et al.: KRAS(G12C) Inhibition with Sotorasib in Advanced Solid Tumors. N Engl J Med 383: 1207-1217, 2020 18. Subbiah V, Kreitman RJ, Wainberg ZA, et al.: Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer. J Clin Oncol 36: 7-13, 2018 13. Garcia-Foncillas J, Bokemeyer C, Italiano A, et al.: Indirect Treatment Comparison of Larotrectinib versus Entrectinib in Treating Patients with TRK Gene Fusion Cancers. Cancers 14: 1793, 2022 17. Shah MH, Wei L, Wirth LJ, et al.: Results of randomized phase II trial of dabrafenib versus dabrafenib plus trametinib in BRAF-mutated papillary thyroid carcinoma. Journal of Clinical Oncology 35: 6022-6022, 2017 16. Falchook GS, Millward M, Hong D, et al.: BRAF inhibitor dabrafenib in patients with metastatic BRAF-mutant thyroid cancer. Thyroid 25: 71-77, 2015 21. Maniakas A, Dadu R, Busaidy NL, et al.: Evaluation of Overall Survival in Patients With Anaplastic Thyroid Carcinoma, 2000-2019. JAMA Oncology 6: 1397-1404, 2020 22. Godbert Y, Henriques de Figueiredo B, Bonichon F, et al.: Remarkable Response to Crizotinib in Woman With Anaplastic Lymphoma Kinase-Rearranged Anaplastic Thyroid Carcinoma. J Clin Oncol 33:e84-87, 2015 5. Wirth LJ, Brose MS, Elisei R, et al.: LIBRETTO-531: a phase III study of selpercatinib in multikinase inhibitor-naïve RET-mutant medullary thyroid cancer. Future Oncology 18: 3143-3150, 2022 19. Subbiah V, Kreitman RJ, Wainberg ZA, et al.: Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: updated analysis from the phase II ROAR basket study. Annals of Oncology 33: 406-415, 2022 4. Wirth LJ, Sherman E, Robinson B, et al.: Efficacy of Selpercatinib in RET-Altered Thyroid Cancers. N Engl J Med 383: 825-835, 2020 9. Drilon A, Laetsch TW, Kummar S, et al.: Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med 378: 731-739, 2018 2. Forsythe A, Zhang W, Phillip Strauss U, et al.: A systematic review and meta-analysis of neurotrophic tyrosine receptor kinase gene fusion frequencies in solid tumors. Ther Adv Med Oncol 12:1758835920975613, 2020 3. Prior IA, Hood FE, Hartley JL: The Frequency of Ras Mutations in Cancer. Cancer Res 80: 2969-2974, 2020 7. Jayson GC, Kerbel R, Ellis LM, et al.: Antiangiogenic therapy in oncology: current status and future directions. Lancet 388: 518-529, 2016 12. Doebele RC, Drilon A, Paz-Ares L, et al.: Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials. Lancet Oncol 21: 271-282, 2020 20. Wang JR, Zafereo ME, Dadu R, et al.: Complete Surgical Resection Following Neoadjuvant Dabrafenib Plus Trametinib in BRAF(V600E)-Mutated Anaplastic Thyroid Carcinoma. Thyroid 29: 1036-1043, 2019 15. Marabelle A, Fakih M, Lopez J, et al.: Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. The Lancet Oncology 21: 1353-1365, 2020 23. Gambacorti-Passerini C, Orlov S, Zhang L, et al.: Long-term effects of crizotinib in ALK-positive tumors (excluding NSCLC): A phase 1b open-label study. Am J Hematol 93: 607-614, 2018 |
| References_xml | – reference: 18. Subbiah V, Kreitman RJ, Wainberg ZA, et al.: Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer. J Clin Oncol 36: 7-13, 2018 – reference: 10. Hong DS, DuBois SG, Kummar S, et al.: Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. The Lancet Oncology 21: 531-540, 2020 – reference: 12. Doebele RC, Drilon A, Paz-Ares L, et al.: Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials. Lancet Oncol 21: 271-282, 2020 – reference: 15. Marabelle A, Fakih M, Lopez J, et al.: Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. The Lancet Oncology 21: 1353-1365, 2020 – reference: 20. Wang JR, Zafereo ME, Dadu R, et al.: Complete Surgical Resection Following Neoadjuvant Dabrafenib Plus Trametinib in BRAF(V600E)-Mutated Anaplastic Thyroid Carcinoma. Thyroid 29: 1036-1043, 2019 – reference: 17. Shah MH, Wei L, Wirth LJ, et al.: Results of randomized phase II trial of dabrafenib versus dabrafenib plus trametinib in BRAF-mutated papillary thyroid carcinoma. Journal of Clinical Oncology 35: 6022-6022, 2017 – reference: 19. Subbiah V, Kreitman RJ, Wainberg ZA, et al.: Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: updated analysis from the phase II ROAR basket study. Annals of Oncology 33: 406-415, 2022 – reference: 23. Gambacorti-Passerini C, Orlov S, Zhang L, et al.: Long-term effects of crizotinib in ALK-positive tumors (excluding NSCLC): A phase 1b open-label study. Am J Hematol 93: 607-614, 2018 – reference: 6. Román-Gil MS, Pozas J, Rosero-Rodríguez D, et al.: Resistance to RET targeted therapy in Thyroid Cancer: Molecular basis and overcoming strategies. Cancer Treatment Reviews 105:102372, 2022 – reference: 25. Dummer R, Schadendorf D, Ascierto PA, et al.: Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 18: 435-445, 2017 – reference: 14. Drilon A, Nagasubramanian R, Blake JF, et al.: A Next-Generation TRK Kinase Inhibitor Overcomes Acquired Resistance to Prior TRK Kinase Inhibition in Patients with TRK Fusion-Positive Solid Tumors. Cancer Discov 7: 963-972, 2017 – reference: 26. Kim TW, Lee J, Kim TM, et al.: 529P A phase Ib trial of belvarafenib in combination with cobimetinib in patients (pts) with RAS- or RAF- mutated (m) solid tumors: Updated safety data and indication-specific efficacy results. Annals of Oncology 32:S595, 2021 – reference: 8. Subbiah V, Cassier PA, Siena S, et al.: Pan-cancer efficacy of pralsetinib in patients with RET fusion-positive solid tumors from the phase 1/2 ARROW trial. Nature Medicine 28: 1640-1645, 2022 – reference: 4. Wirth LJ, Sherman E, Robinson B, et al.: Efficacy of Selpercatinib in RET-Altered Thyroid Cancers. N Engl J Med 383: 825-835, 2020 – reference: 1. Zehir A, Benayed R, Shah RH, et al.: Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med 23: 703-713, 2017 – reference: 13. Garcia-Foncillas J, Bokemeyer C, Italiano A, et al.: Indirect Treatment Comparison of Larotrectinib versus Entrectinib in Treating Patients with TRK Gene Fusion Cancers. Cancers 14: 1793, 2022 – reference: 21. Maniakas A, Dadu R, Busaidy NL, et al.: Evaluation of Overall Survival in Patients With Anaplastic Thyroid Carcinoma, 2000-2019. JAMA Oncology 6: 1397-1404, 2020 – reference: 3. Prior IA, Hood FE, Hartley JL: The Frequency of Ras Mutations in Cancer. Cancer Res 80: 2969-2974, 2020 – reference: 9. Drilon A, Laetsch TW, Kummar S, et al.: Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med 378: 731-739, 2018 – reference: 16. Falchook GS, Millward M, Hong D, et al.: BRAF inhibitor dabrafenib in patients with metastatic BRAF-mutant thyroid cancer. Thyroid 25: 71-77, 2015 – reference: 5. Wirth LJ, Brose MS, Elisei R, et al.: LIBRETTO-531: a phase III study of selpercatinib in multikinase inhibitor-naïve RET-mutant medullary thyroid cancer. Future Oncology 18: 3143-3150, 2022 – reference: 22. Godbert Y, Henriques de Figueiredo B, Bonichon F, et al.: Remarkable Response to Crizotinib in Woman With Anaplastic Lymphoma Kinase-Rearranged Anaplastic Thyroid Carcinoma. J Clin Oncol 33:e84-87, 2015 – reference: 7. Jayson GC, Kerbel R, Ellis LM, et al.: Antiangiogenic therapy in oncology: current status and future directions. Lancet 388: 518-529, 2016 – reference: 24. Hong DS, Fakih MG, Strickler JH, et al.: KRAS(G12C) Inhibition with Sotorasib in Advanced Solid Tumors. N Engl J Med 383: 1207-1217, 2020 – reference: 2. Forsythe A, Zhang W, Phillip Strauss U, et al.: A systematic review and meta-analysis of neurotrophic tyrosine receptor kinase gene fusion frequencies in solid tumors. Ther Adv Med Oncol 12:1758835920975613, 2020 – reference: 11. Waguespack SG, Drilon A, Lin JJ, et al.: Efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma. European Journal of Endocrinology 186: 631-643, 2022 |
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| SubjectTerms | がんゲノム医療 コンパニオン診断薬 マルチキナーゼ阻害薬 個別化治療 甲状腺がん |
| Title | 甲状腺癌に対するゲノム医療 |
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