{"title":"First-line triplet therapy for advanced-stage PIK3CA-mutant HR+ breast cancer improves outcomes","authors":"David Killock","doi":"10.1038/s41571-024-00968-x","DOIUrl":null,"url":null,"abstract":"<p>Approximately 40% of hormone receptor-positive (HR<sup>+</sup>), HER2-negative (HER2<sup>–</sup>) breast cancers harbour activating mutations in <i>PIK3CA</i> (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.</p><p>In INAVO120, 325 patients with metastatic recurrence of <i>PIK3CA</i>-mutant HR<sup>+</sup>, HER2<sup>–</sup> 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.</p>","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":81.1000,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Reviews Clinical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41571-024-00968-x","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
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.
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.