Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study
Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study
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DOI：
10.1200/jco.2017.75.3780
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发表时间：
2018-02-20
影响因子：
45.3
通讯作者：
Kurzrock, Razelle
中科院分区：
文献类型：
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作者：
Hainsworth, John D.;Meric-Bernstam, Funda;Kurzrock, Razelle
目的检测肿瘤中特定的分子改变，指导几种类型癌症患者选择有效的靶向治疗。这些分子改变可能发生在靶向治疗效果尚不清楚的其他肿瘤类型中。MyPathway研究评估了在肿瘤类型中选择靶向治疗的有效性和安全性，这些肿瘤类型包含相关的遗传改变，但目前这些治疗的标签之外。smypathway （ClinicalTrials.gov标识符：NCT02091141）是一项多中心、非随机、IIa期多篮子研究。具有人表皮生长因子受体-2、表皮生长因子受体、v-raf鼠肉瘤病毒癌基因同源物B1或Hedgehog通路分子改变的晚期难治性实体肿瘤患者分别用pertuzumab联合曲妥珠单抗、厄洛替尼、vemurafenib或vismodegib治疗。主要终点是研究者在每个肿瘤通路队列中评估的客观缓解率。结果2014年4月1日至2016年11月1日，共有35种不同肿瘤类型的251例患者接受了研究治疗。疗效人群包括230名接受治疗的患者，在评估前评估其疗效或停止治疗。14种不同肿瘤类型的52例（23%）患者客观缓解（完全缓解，n = 4；部分缓解，n = 48）。客观反应率显著的肿瘤通路队列包括人表皮生长因子受体2扩增/过表达的结直肠癌（38% [14 / 37];95% CI， 23%至55%）和v-raf小鼠肉瘤病毒癌基因同源B1 v600突变的非小细胞肺癌（43% [14 / 6];95% CI， 18%至71%）。结论：在MyPathway研究中，目前批准的四种靶向治疗方案在不使用化疗的情况下，对几种目前未标记为这些药物的难治性实体肿瘤类型产生了有意义的反应。
PurposeDetection of specific molecular alterations in tumors guides the selection of effective targeted treatment of patients with several types of cancer. These molecular alterations may occur in other tumor types for which the efficacy of targeted therapy remains unclear. The MyPathway study evaluates the efficacy and safety of selected targeted therapies in tumor types that harbor relevant genetic alterations but are outside of current labeling for these treatments.MethodsMyPathway (ClinicalTrials.gov identifier: NCT02091141) is a multicenter, nonrandomized, phase IIa multiple basket study. Patients with advanced refractory solid tumors harboring molecular alterations in human epidermal growth factor receptor-2, epidermal growth factor receptor, v-raf murine sarcoma viral oncogene homolog B1, or the Hedgehog pathway are treated with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. The primary end point is investigator-assessed objective response rate within each tumor-pathway cohort.ResultsBetween April 1, 2014 and November 1, 2016, 251 patients with 35 different tumor types received study treatment. The efficacy population contains 230 treated patients who were evaluated for response or discontinued treatment before evaluation. Fifty-two patients (23%) with 14 different tumor types had objective responses (complete, n = 4; partial, n = 48). Tumor-pathway cohorts with notable objective response rates included human epidermal growth factor receptor-2-amplified/overexpressing colorectal (38% [14 of 37]; 95% CI, 23% to 55%) and v-raf murine sarcoma viral oncogene homolog B1 V600-mutated non-small-cell lung cancer (43% [six of 14]; 95% CI, 18% to 71%).ConclusionThe four currently approved targeted therapy regimens in the MyPathway study produced meaningful responses when administered without chemotherapy in several refractory solid tumor types not currently labeled for these agents.