Survival in advanced GIST has improved over time and correlates with increased access to post-imatinib tyrosine kinase inhibitors: results from Life Raft Group Registry.

Clinical Sarcoma Research Pub Date : 2019-04-02 eCollection Date: 2019-01-01 DOI:10.1186/s13569-019-0114-5
Jerry W Call, Yu Wang, Denisse Montoya, Norman J Scherzer, Michael C Heinrich
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引用次数: 20

Abstract

Background: The use of imatinib, sunitinib, and regorafenib has transformed the treatment of advanced GIST. Sunitinib and regorafenib improve progression free-survival in the second (2L) and third (3L) line, respectively, compared with placebo. However, the impact of these agents on overall survival (OS) is unclear.

Methods: The Life Raft Group (LRG) patient registry contains records from 1716 GIST patients; 526 have advanced to at least 2L treatment. Patient-reported treatment and outcome data were examined to determine treatment patterns and their impact on OS.

Results: Median OS from start of 2L therapy was 32.4 months for sunitinib (n = 436) compared with 27.1 months for patients treated with any other 2L drug (n = 74, p = 0.023, HR 1.377) and 16.8 months for patients who never received sunitinib in any treatment line (n = 42, p = 0.028, HR 1.52). In patients reporting progression in 2L, the median OS in patients subsequently receiving 3L regorafenib (n = 53, 26.2 months) was longer than that of 3L patients who never received regorafenib in any line of therapy (n = 174, 14.3 months, p = 0.0002, HR 2.231), and was longer than that of patients who received any other 3L treatment (19.8 months, p = 0.044, HR 1.525). OS for advanced GIST patients in the LRG registry has improved over time (p = 0.0013), correlated with the increased use of TKIs in ≥ 2L settings.

Conclusions: In our analysis, sunitinib and regorafenib significantly improved OS compared with patients who never received these agents. Our data also support the hypothesis that the use of KIT/PDGFRA inhibitors, including non-approved agents, has improved OS for patients with imatinib- and sunitinib-resistant GIST.

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晚期GIST的生存率随着时间的推移而提高,并且与伊马替尼后酪氨酸激酶抑制剂的使用增加相关:来自Life Raft Group Registry的结果。
背景:伊马替尼、舒尼替尼和瑞非尼的使用已经改变了晚期GIST的治疗。与安慰剂相比,舒尼替尼和瑞戈非尼分别改善了第二(2L)和第三(3L)线的无进展生存期。然而,这些药物对总生存期(OS)的影响尚不清楚。方法:救生筏组(LRG)患者登记包含来自1716名GIST患者的记录;526例已经进展到至少2L的治疗。检查患者报告的治疗和结果数据,以确定治疗模式及其对OS的影响。结果:从2L治疗开始,舒尼替尼的中位OS为32.4个月(n = 436),而接受任何其他2L药物治疗的患者为27.1个月(n = 74, p = 0.023, HR 1.377),从未接受过舒尼替尼治疗的患者为16.8个月(n = 42, p = 0.028, HR 1.52)。在报告2L进展的患者中,随后接受3L瑞非尼治疗的患者的中位OS (n = 53, 26.2个月)长于未接受任何治疗的3L患者(n = 174, 14.3个月,p = 0.0002, HR 2.231),长于接受任何其他3L治疗的患者(19.8个月,p = 0.044, HR 1.525)。LRG登记的晚期GIST患者的OS随着时间的推移而改善(p = 0.0013),这与TKIs在≥2L患者中的使用增加相关。结论:在我们的分析中,与从未接受过这些药物的患者相比,舒尼替尼和瑞非尼显著改善了OS。我们的数据也支持KIT/PDGFRA抑制剂(包括未经批准的药物)的使用改善了伊马替尼和舒尼替尼耐药GIST患者的OS的假设。
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期刊介绍: Clinical Sarcoma Research considers for publication articles related to research on sarcomas, including both soft tissue and bone. The journal publishes original articles and review articles on the diagnosis and treatment of sarcomas along with new insights in sarcoma research, which may be of immediate or future interest for diagnosis and treatment. The journal also considers negative results, especially those from studies on new agents, as it is vital for the medical community to learn whether new agents have been proven effective or ineffective within subtypes of sarcomas. The journal also aims to offer a forum for active discussion on topics of major interest for the sarcoma community, which may be related to both research results and methodological topics.
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