Off-label use of targeted therapies in osteosarcomas: data from the French registry OUTC'S (Observatoire de l'Utilisation des Therapies Ciblees dans les Sarcomes)
Off-label use of targeted therapies in osteosarcomas: data from the French registry OUTC'S (Observatoire de l'Utilisation des Therapies Ciblees dans les Sarcomes)
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DOI：
10.1186/s12885-015-1894-5
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发表时间：
2015-11-05
期刊：
影响因子：
3.8
通讯作者：
Marec-Berard, Perrine
中科院分区：
文献类型：
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作者：
Penel-Page, Mathilde;Ray-Coquard, Isabelle;Marec-Berard, Perrine
背景资料：本研究的目的是探索法国肉瘤组-骨肿瘤研究组注册的骨肉瘤患者的靶向治疗（TT）的标签外用药方法：对2009年1月1日至2013年7月15日期间登记的所有骨肉瘤患者进行分析。29例难治性复发性骨肉瘤患者接受了33种TT治疗。治疗开始时的中位年龄为19岁（范围9-72岁）。既往化疗线的中位数为3（范围1-8）。入选前，3例患者处于第二次完全缓解，26例患者因转移性复发而进展。23例患者接受西罗莫司（18例联合环磷酰胺）; 5例舒尼替尼; 4例索拉非尼; 1例帕唑帕尼。观察到45.5%的患者病情稳定（95%置信区间（CI）[20-52.8]）。接受西罗莫司治疗的患者的中位无进展生存期（PFS）为3个月（95% CI [2-5.4]），接受多靶向酪氨酸激酶抑制剂治疗的患者为1.8个月（95% CI [1.3-2.8]）; 6个月PFS 15%。中位总生存期（OS）为6.8个月（95% CI [4.7-12.1]），1年OS为24%。在多变量分析中，接受西罗莫司治疗的患者的PFS上级其他TT（风险比（HR）= 2.7，95% CI [1.05-7.1]）。未报告中毒性死亡。3级和4级毒性分别观察到27和6%的cases.Conclusion：标签外TT，特别是西罗莫司，在治疗难治性骨肉瘤，包括在儿科人群中具有可接受的毒性特征的好处。
Background: The objective of this study is to explore the off-label use of targeted therapies (TTs) for patients with osteosarcoma registered within the French Sarcoma Group -Bone Tumor Study Group (GSF-GETO) national registry.Methods: All patients with an osteosarcoma, registered between January 1, 2009 and July 15, 2013 were analyzed.Results: Twenty-nine patients with refractory relapsed osteosarcomas received 33 treatment lines of TTs. The median age at the beginning of treatment was 19 years (range 9-72). The median number of previous lines of chemotherapy was 3 (range 1-8). Before inclusion, 3 patients were in second complete remission, 26 were in progression for metastatic relapse. Twenty-three patients received sirolimus (in combination with cyclophosphamide for 18); 5, sunitinib; 4, sorafenib; and one, pazopanib. Stable disease was observed for 45.5 % of patients (95 % Confidence Interval (CI) [20-52.8]). The median Progression-Free Survival (PFS) was 3 months (95 % CI [2-5.4]) for patients treated by sirolimus and 1.8 months (95 % CI [1.3-2.8]) for patients receiving multi-targeted tyrosine kinase inhibitors; 6-month PFS 15 %. The median Overall Survival (OS) was 6.8 months (95 % CI [4.7-12.1]), and one-year OS was 24 %. In a multivariate analysis, PFS was superior for patients receiving sirolimus compared to other TTs (Hazard Ratio (HR) = 2.7, 95 % CI [1.05-7.1]). No toxic death was reported. Grade 3 and 4 toxicities were observed in 27 and 6 % of cases respectively.Conclusion: Off-label TTs, especially sirolimus, reported benefit in the treatment of refractory osteosarcomas with an acceptable toxicity profile, including in pediatric population.