Department of Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
Department of Internal Medicine, Temple University Hospital, Philadelphia, PA, USA.
Curr Treat Options Oncol. 2022 May;23(5):749-761. doi: 10.1007/s11864-022-00958-0. Epub 2022 Mar 28.
In our practice, we evaluate the mutation status of advanced unresectable disease to guide decisions on use of tyrosine kinase inhibitor (TKI) therapy. This review focuses on management of GIST with KIT and PDGFRA mutations. Imatinib is first-line treatment for unresectable gastrointestinal stromal tumors (GISTs) unless they harbor a PDGFRA D842V mutation; it is recommended to escalate imatinib to twice daily dosing for KIT exon 9 mutant tumors. When patients progress on first-line treatment, treatment is changed to sunitinib followed by regorafenib; while the spectrum of activity against resistance mutations varies with these agents, routine biopsies provide data on one area of disease and ctDNA has not been validated prospectively. For those with a PDGFRA D842V mutation, avapritinib is the first TKI to lead to tumor response and disease control. Ripretinib is approved in the 4th line setting, with limited data on its benefit for PDGFRA D842V GIST. Avapritinib can be considered for treatment beyond ripretinib for KIT mutant disease. The efficacy of other TKIs tested in GIST is reviewed. Ongoing therapy provides palliative benefit and should be continued given rapid decline observed off of treatment.
在我们的实践中，我们评估晚期不可切除疾病的突变状态，以指导酪氨酸激酶抑制剂（TKI）治疗的决策。本综述重点介绍 KIT 和 PDGFRA 突变的 GIST 管理。伊马替尼是不可切除胃肠道间质瘤（GIST）的一线治疗药物，除非它们携带 PDGFRA D842V 突变；建议对 KIT 外显子 9 突变肿瘤增加伊马替尼的每日剂量。当患者在一线治疗中进展时，治疗方案更改为舒尼替尼，然后是regorafenib；虽然这些药物对耐药突变的作用范围不同，但常规活检提供了疾病的一个区域的数据，而 ctDNA 尚未前瞻性验证。对于携带 PDGFRA D842V 突变的患者，avapritinib 是首个导致肿瘤反应和疾病控制的 TKI。ripretinib 被批准用于四线治疗，其对 PDGFRA D842V GIST 的益处数据有限。对于 KIT 突变疾病，avapritinib 可被考虑用于 ripretinib 之后的治疗。其他在 GIST 中测试的 TKI 的疗效进行了回顾。正在进行的治疗提供了姑息性的益处，并且鉴于治疗后观察到的快速下降，应该继续进行治疗。
