A 5-year review of genomic medicine in breast cancer: insights from C-CAT data on 3776 Japanese patients.

IF 4 3区医学 Q1 OBSTETRICS & GYNECOLOGY

Breast Cancer Pub Date : 2024-12-04 DOI:10.1007/s12282-024-01656-5

Midori Morita, Ryo Tsunashima, Tetsuhiro Yoshinami, Masaki Ishida, Masahiro Iwasaku, Sae Kitano, Chikage Kato, Koichi Sakaguchi, Koichi Takayama, Yasuto Naoi

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引用次数: 0

Abstract

Background: In Japan, despite 5 years since CGP tests were covered by insurance in 2019, low drug accessibility rates remain a critical issue. We evaluated drug accessibility in 3776 breast cancer from the C-CAT database using two criteria: the proportion first linked to PMDA-approved drugs with phase III trial evidence for breast cancer through CGP tests but not existing Companion diagnostics [CDx] (*), and the proportion first linked to PMDA-approved drugs including based on phase I and II trial evidence (**). Additionally, cases linked to investigational drugs for non-PMDA-approved drugs were counted.

Methods: We identified the top 100 genetic alterations in Japanese breast cancer via CGP tests, listing corresponding drugs from C-CAT reports. Drug accessibility was re-evaluated through simulations with updated evidence levels by a member of the expert panel at Osaka University (EP-EL in OUH).

Results: Results showed the proportion improved to 28.4% under the newest EP-EL in OUH, including 3.4% for HER2-negative cases eligible for HER2-targeted therapy due to ERBB2 amplification and 25.0% for ER-positive, HER2-negative cases eligible for capivasertib-fulvestrant therapy due to PIK3CA, AKT1, and PTEN alterations (*). However, in part, initial false negatives for HER2 status and practical difficulties in using CGP tests as a CDx for capivasertib exist. Including mutations like TMB-H, MSI-H, BRAF V600E mutation, and NTRK fusions raised the proportion to 37.9% (**), but lacking drugs with phase III trials evidence.

Conclusion: These findings highlight the ongoing difficulties in demonstrating clear clinical utility of CGP tests in Japan, emphasizing the need for broad discussions on its future direction.

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乳腺癌基因组医学的5年回顾：来自3776名日本患者C-CAT数据的见解

背景：在日本，尽管自2019年CGP检测被纳入保险已有5年时间，但药物可及性低仍然是一个关键问题。我们使用两个标准评估了C-CAT数据库中3776例乳腺癌患者的药物可及性：首先与pmda批准的药物相关的比例（通过CGP测试，但不存在伴随诊断[CDx]），以及首先与pmda批准的药物相关的比例（包括基于I期和II期试验证据）。此外，与未经pmda批准的研究药物相关的病例也被统计在内。方法：我们通过CGP检测确定了日本乳腺癌的前100个基因改变，并列出了C-CAT报告中相应的药物。大阪大学专家小组的一名成员（EP-EL in OUH）通过具有最新证据水平的模拟重新评估了药物可及性。结果：结果显示，在最新的EP-EL下，OUH的比例提高到28.4%，其中her2阴性患者因ERBB2扩增而适合her2靶向治疗的比例为3.4%，er阳性、her2阴性患者因PIK3CA、AKT1和PTEN改变而适合capivasertib-fulvestrant治疗的比例为25.0%（*）。然而，在某种程度上，HER2状态的初始假阴性和使用CGP测试作为capivasertib的CDx存在实际困难。包括TMB-H、MSI-H、BRAF V600E突变和NTRK融合等突变的比例提高到37.9%(**)，但缺乏具有III期试验证据的药物。结论：这些发现突出了在日本证明CGP试验的明确临床应用的持续困难，强调了对其未来方向进行广泛讨论的必要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Breast Cancer ONCOLOGY-OBSTETRICS & GYNECOLOGY

CiteScore

6.70

自引率

2.50%

发文量

105

审稿时长

6-12 weeks

期刊介绍： Breast Cancer, the official journal of the Japanese Breast Cancer Society, publishes articles that contribute to progress in the field, in basic or translational research and also in clinical research, seeking to develop a new focus and new perspectives for all who are concerned with breast cancer. The journal welcomes all original articles describing clinical and epidemiological studies and laboratory investigations regarding breast cancer and related diseases. The journal will consider five types of articles: editorials, review articles, original articles, case reports, and rapid communications. Although editorials and review articles will principally be solicited by the editors, they can also be submitted for peer review, as in the case of original articles. The journal provides the best of up-to-date information on breast cancer, presenting readers with high-impact, original work focusing on pivotal issues.