Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Institute - Oncology Center, Roentgena 5, 02-781 Warsaw, Poland.
Early Phase Clinical Trial Unit, Maria Sklodowska-Curie Institute - Oncology Center; Roentgena 5, 02-781 Warsaw, Poland.
J Geriatr Oncol. 2018 Sep;9(5):520-525. doi: 10.1016/j.jgo.2018.03.009. Epub 2018 Mar 27.
The aim of the study was to analyze the treatment results of advanced GIST in the largest, homogenous series of older patients.
Between 2001 and 2016, 686 patients with metastatic/unresectable GIST were treated initially with imatinib and 656 were included in the analysis. Subsequently 232 patients were treated with sunitinib after imatinib failure. We have analyzed the outcomes of patients who have been treated with the tyrosine kinase inhibitor at the age ≥ 70 years and compared to control group of patients younger than 70 years old.
In the group of patients treated with imatinib, 139 (21%) started therapy at the age of at least 70 years (median age of the entire cohort: 60). Median progression-free survival (PFS) on 1st line imatinib did not differ between patients ≥70 yo (years old) and < 70yo (38.5 vs 44.9 months), but median overall survival (OS) was significantly better for younger patients (81 months vs. 50; p = 0.0001; although disease-specific survival - DSS was similar). Distribution of primary tumor mutational status was generally similar in older and younger patients. Permanent dose reduction (300-100 mg/day) was required for 23 patients (16.9%) in the older group and was significantly more frequent as compared to younger patients (5%). Drug-related adverse events were mainly of grades 1/2, but grade 3/4 toxicity occurred more frequently in older (14.7%) than in younger patients (3.8%). Similarly in group of patients treated with second-line sunitinib median PFS and DSS were comparable in groups of patients ≥70 yo (n = 55) and < 70yo (9.7 months vs 10.3 months; p = 0.7, and 21.5 vs 22.9 months). >40% of patients in both groups required dose adjustments to 37.5-25 mg daily.
Our study confirms that current therapy of advanced GIST with tyrosine kinase inhibitors (both in 1st and 2nd line) in older patients enable to achieve the similar disease control rate and final outcomes as in younger patients, but it demands close cooperation of experienced oncologist with patients for dose modifications and side effects management. Limitation of our study is that the patients did not undergo a comprehensive geriatric assessment, what might be helpful for personalized management of patients. Nevertheless, we confirm that older patients with GIST should not receive less treatment irrespective of comorbidities.
本研究旨在分析最大的同质老年患者群体中晚期 GIST 的治疗结果。
2001 年至 2016 年，686 例转移性/不可切除 GIST 患者接受伊马替尼初始治疗，其中 656 例纳入分析。随后，232 例伊马替尼耐药患者接受舒尼替尼治疗。我们分析了年龄≥70 岁的接受酪氨酸激酶抑制剂治疗的患者的结果，并与年龄<70 岁的对照组患者进行了比较。
在接受伊马替尼治疗的患者中，139 例（21%）年龄至少为 70 岁（整个队列的中位年龄：60 岁）。一线伊马替尼治疗的无进展生存期（PFS）在≥70 岁的患者（38.5 个月）和<70 岁的患者（44.9 个月）之间没有差异，但年轻患者的总生存期（OS）显著更好（81 个月 vs. 50 个月；p=0.0001；尽管疾病特异性生存率-DSS 相似）。年龄较大和较小患者的原发肿瘤突变状态分布总体相似。在年龄较大的组中，23 例（16.9%）需要永久减少剂量（300-100mg/天），这一比例明显高于年龄较小的患者（5%）。药物相关不良事件主要为 1/2 级，但 3/4 级毒性在年龄较大的患者（14.7%）中比在年龄较小的患者（3.8%）中更常见。同样，在接受二线舒尼替尼治疗的患者中，≥70 岁组（n=55）和<70 岁组的中位 PFS 和 DSS 相似（9.7 个月 vs. 10.3 个月；p=0.7，21.5 个月 vs. 22.9 个月）。两组中均有>40%的患者需要将剂量调整为 37.5-25mg/天。
我们的研究证实，晚期 GIST 患者目前采用酪氨酸激酶抑制剂（一线和二线）进行治疗，可获得与年轻患者相似的疾病控制率和最终结局，但需要经验丰富的肿瘤学家与患者密切合作，以调整剂量和处理副作用。本研究的局限性在于患者未接受全面的老年评估，这可能有助于患者的个体化管理。尽管如此，我们仍证实，无论合并症如何，老年 GIST 患者均不应接受较少的治疗。
