First-line triplet therapy for advanced-stage PIK3CA-mutant HR+ breast cancer improves outcomes

IF 81.1 1区 医学 Q1 ONCOLOGY Nature Reviews Clinical Oncology Pub Date : 2024-11-12 DOI:10.1038/s41571-024-00968-x
David Killock
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Abstract

Approximately 40% of hormone receptor-positive (HR+), HER2-negative (HER2) breast cancers harbour activating mutations in PIK3CA (encoding the catalytic subunit of PI3Kα); these mutations are generally associated with a poor prognosis but also responsiveness to inhibitors of the PI3K–AKT pathway. Now, data from the phase III INAVO120 trial demonstrate that addition of the selective PI3Kα inhibitor and degrader inavolisib to standard-of-care first-line endocrine plus CDK4/6 inhibitor therapy for advanced-stage disease is feasible and increases efficacy.

In INAVO120, 325 patients with metastatic recurrence of PIK3CA-mutant HR+, HER2 breast cancer during, or within 12 months of completing, adjuvant endocrine-based therapy were randomly assigned (1:1) to receive palbociclib and fulvestrant plus either inavolisib or placebo. The requirement for early disease relapse enriched for patients with a poor prognosis: 83% had received chemotherapy, 80% had visceral metastases, 52% had liver metastases and 51% had ≥3 metastases. Notably, however, only 1% of patients had received a CDK4/6 inhibitor as part of adjuvant therapy. Progression-free survival (PFS) was the primary end point.

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晚期PIK3CA突变HR+乳腺癌一线三联疗法可改善疗效
约40%的激素受体阳性(HR+)、HER2阴性(HER2-)乳腺癌存在PIK3CA(编码PI3Kα的催化亚基)激活突变;这些突变通常与预后不良有关,但也与对PI3K-AKT通路抑制剂的反应性有关。现在,Ⅲ期INAVO120试验的数据表明,在治疗晚期疾病的一线内分泌加CDK4/6抑制剂标准疗法中加入选择性PI3Kα抑制剂和降解剂inavolisib是可行的,而且能提高疗效。在INAVO120研究中,325名PIK3CA突变HR+、HER2-乳腺癌转移性复发患者在接受辅助内分泌治疗期间或完成治疗后12个月内被随机分配(1:1)接受palbociclib和氟维司群加inavolisib或安慰剂治疗。预后较差的患者需要接受早期疾病复发治疗:83%的患者接受过化疗,80%的患者有内脏转移,52%的患者有肝转移,51%的患者有≥3个转移灶。但值得注意的是,只有1%的患者在辅助治疗中使用过CDK4/6抑制剂。无进展生存期(PFS)是主要终点。
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来源期刊
CiteScore
99.40
自引率
0.40%
发文量
114
审稿时长
6-12 weeks
期刊介绍: Nature Reviews publishes clinical content authored by internationally renowned clinical academics and researchers, catering to readers in the medical sciences at postgraduate levels and beyond. Although targeted at practicing doctors, researchers, and academics within specific specialties, the aim is to ensure accessibility for readers across various medical disciplines. The journal features in-depth Reviews offering authoritative and current information, contextualizing topics within the history and development of a field. Perspectives, News & Views articles, and the Research Highlights section provide topical discussions, opinions, and filtered primary research from diverse medical journals.
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