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
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
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DOI：
10.1186/s13569-019-0114-5
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发表时间：
2019-04-02
影响因子：
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通讯作者：
Heinrich, Michael C.
中科院分区：
文献类型：
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作者：
Call, Jerry W.;Wang, Yu;Heinrich, Michael C.
背景 伊马替尼、舒尼替尼和瑞格非尼的使用改变了晚期 GIST 的治疗。与安慰剂相比，舒尼替尼和瑞格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 Life Raft Group (LRG) 患者登记处包含 1716 名 GIST 患者的记录； 526 名患者已进展至至少 2L 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 舒尼替尼 (n=436) 开始 2L 治疗后的中位 OS 为 32.4 个月，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)，从未在任何治疗线接受过舒尼替尼的患者为 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 瑞戈非尼治疗的患者的中位 OS（n=53，26.2 个月）长于从未接受过任何治疗的 3L 患者的中位 OS（n=174，14.3 个月，p=0.0002，HR 2.231），并且长于接受任何其他 3L 治疗的患者的中位 OS（19.8 个月，19.8 个月）。 p=0.044，HR 1.525）。 LRG 登记中的晚期 GIST 患者的 OS 随着时间的推移而有所改善 (p=0.0013)，与 >= 2L 环境中 TKI 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，舒尼替尼和瑞格非尼显着改善了 OS。我们的数据还支持这样的假设：使用 KIT/PDGFRA 抑制剂（包括未经批准的药物）可以改善伊马替尼和舒尼替尼耐药的 GIST 患者的 OS。
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.