Purpose Detection 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. Methods MyPathway ( 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. Results Between 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%). Conclusion The 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.

中文翻译：

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基于分子特征的晚期实体瘤靶向治疗：来自 MyPathway 的结果，一项开放标签的 IIa 期多篮研究

目的 检测肿瘤中的特定分子改变可指导对多种类型癌症患者进行有效靶向治疗的选择。这些分子改变可能发生在靶向治疗的疗效尚不清楚的其他肿瘤类型中。MyPathway 研究评估了选定的靶向治疗在具有相关基因改变但不在这些治疗当前标签范围内的肿瘤类型中的有效性和安全性。方法 MyPathway（ClinicalTrials.gov 标识符：NCT02091141）是一项多中心、非随机、IIa 期多篮子研究。在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 中存在分子改变的晚期难治性实体瘤患者，或 Hedgehog 通路分别用帕妥珠单抗加曲妥珠单抗、厄洛替尼、威罗菲尼或 vismodegib 治疗。主要终点是每个肿瘤通路队列中研究者评估的客观反应率。结果 2014 年 4 月 1 日至 2016 年 11 月 1 日期间，251 名患有 35 种不同肿瘤类型的患者接受了研究治疗。疗效人群包含 230 名接受治疗的患者，这些患者在评估前接受了反应评估或停止治疗。具有 14 种不同肿瘤类型的 52 名患者 (23%) 有客观反应（完全，n = 4；部分，n = 48）。具有显着客观反应率的肿瘤途径队列包括人表皮生长因子受体 2 扩增/过度表达的结直肠癌（38% [14 of 37]；95% CI，23% 至 55%）和 v-raf 鼠肉瘤病毒癌基因同源物 B1 V600 突变的非小细胞肺癌（43% [14 个中的 6 个]；95% CI，18% 至 71%）。结论 MyPathway 研究中目前批准的四种靶向治疗方案在没有化疗的情况下在几种目前未标记为这些药物的难治性实体瘤类型中产生了有意义的反应。