■SOLTI-1301AGATA研究旨在评估多机构分子筛查计划的可行性,以更好地表征晚期乳腺癌(ABC)的基因组景观,并促进患者获得匹配的靶向治疗在西班牙。
■在三个不同的实验室中使用具有三个不同基因面板的FFPE肿瘤样品对74个癌症相关基因进行DNA测序。多学科咨询委员会前瞻性地推荐潜在的靶向治疗。主要目的是确定将体细胞DNA改变与实验药物/药物类别相匹配的成功。
■2014年9月至2017年7月,纳入了来自10个机构的305名ABC患者。260例(85.3%)患者肿瘤测序成功。中位年龄为54岁(29-80岁);大多数肿瘤为激素受体阳性/HER2阴性(74%),其次是三阴性(14.5%)和HER2阳性(11.5%)。分析的97个(37%)肿瘤样品来自转移部位。在163例(62.7%)患者中发现体细胞突变,主要在PIK3CA(34%),TP53(22%),AKT1(5%),ESR1(3%),和ERBB2(3%)基因。在转移性样品与原发性样品中观察到AKT1突变的显着富集(9%与2%;p=0.01)。45%(n=116)成功筛查的患者推荐使用基因组驱动的癌症治疗。其中11%(n=13)最终收到了它。在这些患者中,46.2%的患者在匹配治疗后的PFS≥6个月。
■AGATA是在西班牙进行的第一个全国性的分子筛选计划,我们证明了在ABC管理中实施分子数据是可行的。虽然这些结果很有希望,只有11%的患者接受了基因组驱动的癌症治疗.
UNASSIGNED: The SOLTI-1301 AGATA study aimed to assess the feasibility of a multi-institutional molecular screening program to better characterize the genomic landscape of advanced breast cancer (ABC) and to facilitate patient access to matched-targeted therapies in Spain.
UNASSIGNED: DNA sequencing of 74 cancer-related genes was performed using FFPE tumor samples in three different laboratories with three different gene panels. A multidisciplinary advisory board prospectively recommended potential targeted treatments. The primary objective was to determine the success of matching somatic DNA alteration to an experimental drug/drug class.
UNASSIGNED: Between September 2014 and July 2017, 305 patients with ABC from 10 institutions were enrolled. Tumor sequencing was successful in 260 (85.3%) patients. Median age was 54 (29-80); most tumors were hormone receptor-positive/HER2-negative (74%), followed by triple-negative (14.5%) and HER2-positive (11.5%). Ninety-seven (37%) tumor samples analyzed proceeded from metastatic sites. Somatic mutations were identified in 163 (62.7%) patients, mostly in PIK3CA (34%), TP53 (22%), AKT1 (5%), ESR1 (3%), and ERBB2 (3%) genes. Significant enrichment of AKT1 mutation was observed in metastatic versus primary samples (9% vs. 2%; p=0.01). Genome-driven cancer therapy was recommended in 45% (n=116) of successfully screened patients, 11% (n=13) of whom finally received it. Among these patients, 46.2% had a PFS of ≥6 months on matched therapy.
UNASSIGNED: AGATA is the first nationwide molecular screening program carried out in Spain and we proved that implementing molecular data in the management of ABC is feasible. Although these results are promising, only 11% of the patients with genome-driven cancer therapy received it.