Final analyses of OPTiM: a randomized phase III trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in unresectable stage III- IV melanoma
Final analyses of OPTiM: a randomized phase III trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in unresectable stage III- IV melanoma
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DOI：
10.1186/s40425-019-0623-z
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发表时间：
2019-06-06
影响因子：
10.9
通讯作者：
Kaufman, Howard L.
中科院分区：
文献类型：
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作者：
Andtbacka, Robert H., I;Collichio, Frances;Kaufman, Howard L.
背景：Laherparepvec是一种溶瘤免疫疗法，已在美国、欧洲、澳大利亚和瑞士获得批准。我们报告的最后计划分析OPTIM，一个随机开放标签的III期临床试验，在患者与不可切除的IIIB-IVM 1C期melanoma.Methods：患者被随机2：1接受瘤内talumogene laherparepvec或皮下重组GM-CSF。除总生存期（OS）外，还报告了持久缓解率（DRR）、客观缓解率（ORR）、完全缓解（CR）和安全性。所有的最终分析被认为是描述性的和治疗反应进行了评估，由investigator.Results：436例患者的意向治疗人群中，295人被分配到talimogene laherparepvec和141 GM-CSF。最终OS分析的中位随访时间为49个月。拉他莫基组和GM-CSF组的中位OS分别为23.3个月（95%置信区间[CI]，19.5-29.6）和18.9个月（95% CI，16.0-23.7）（未分层风险比，0.79; 95% CI，0.62-1.00; p = 0.0494 [描述性]）。DRR分别为19.0和1.4%（未校正比值比，16.6; 95% CI，4.0-69.2; p < 0.0001）; ORR分别为31.5和6.4%。拉他莫基组和GM-CSF组分别有50例（16.9%）和1例（0.7%）患者达到CR。在拉他莫基治疗的患者中，中位CR时间为8.6个月;未达到中位CR持续时间。在CR患者中，估计有88.5%的患者在5年里程碑分析时存活。如主要分析中所述，拉氏替尼在IIIB-IVM 1a期黑色素瘤中的疗效更明显。安全性报告是一致的主要OPTiM analysis.Conclusions：在这个最终计划OPTiM分析，talimogene laherparepvec继续导致改善的长期疗效与GM-CSF，并保持良好的耐受性。最终分析还证实，拉他莫基与持久CR相关，持久CR与生存期延长相关。
Background: Talimogene laherparepvec is an oncolytic immunotherapy approved in the US, Europe, Australia and Switzerland. We report the final planned analysis of OPTiM, a randomized open-label phase III trial in patients with unresectable stage IIIB-IVM1c melanoma.Methods: Patients were randomized 2:1 to receive intratumoral talimogene laherparepvec or subcutaneous recombinant GM-CSF. In addition to overall survival (OS), durable response rate (DRR), objective response rate (ORR), complete responses (CR), and safety are also reported. All final analyses are considered to be descriptive and treatment responses were assessed by the investigators.Results: Of 436 patients in the intent-to-treat population, 295 were allocated to talimogene laherparepvec and 141 to GM-CSF. Median follow-up in the final OS analysis was 49 months. Median OS was 23.3 months (95% confidence interval [CI], 19.5-29.6) and 18.9 months (95% CI, 16.0-23.7) in the talimogene laherparepvec and GM-CSF arms, respectively (unstratified hazard ratio, 0.79; 95% CI, 0.62-1.00; p = 0.0494 [descriptive]). DRR was 19.0 and 1.4% (unadjusted odds ratio, 16.6; 95% CI, 4.0-69.2; p < 0.0001); ORR was 31.5 and 6.4%. Fifty (16.9%) and 1 (0.7%) patient in the talimogene laherparepvec and GM-CSF arms, respectively, achieved CR. In talimogene laherparepvec-treated patients, median time to CR was 8.6 months; median CR duration was not reached. Among patients with a CR, 88.5% were estimated to survive at a 5-year landmark analysis. Talimogene laherparepvec efficacy was more pronounced in stage IIIB-IVM1a melanoma as already described in the primary analysis. The safety reporting was consistent with the primary OPTiM analysis.Conclusions: In this final planned OPTiM analysis, talimogene laherparepvec continued to result in improved longer-term efficacy versus GM-CSF and remained well tolerated. The final analysis also confirms that talimogene laherparepvec was associated with durable CRs that were associated with prolonged survival.