{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T01:16:05Z","timestamp":1793236565752,"version":"4.5.0"},"reference-count":16,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"34","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      The US Food and Drug Administration (FDA) approved capivasertib in combination with fulvestrant for adult patients with hormone receptor\u2013positive, human epidermal growth factor receptor 2 (HER2)\u2013negative, locally advanced, or metastatic breast cancer (MBC) who have received at least one previous endocrine therapy and whose tumors harbor one or more phosphatidylinositol 3-kinase (\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      )\/AKT Serine\/Threonine Kinase 1 (\n                      <jats:italic>AKT1<\/jats:italic>\n                      )\/phosphatase and tensin homolog (\n                      <jats:italic>PTEN<\/jats:italic>\n                      ) alterations, as detected by an FDA-approved test.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>\n                      Approval was based on CAPItello-291, a randomized, double-blind, multicenter trial of 708 patients with hormone receptor\u2013positive, HER2-negative advanced or MBC, including 289 patients with\n                      <jats:italic>PIK3CA\/AKT1\/PTEN<\/jats:italic>\n                      tumor alterations. Patients were randomly assigned 1:1 to receive capivasertib 400 mg twice daily for 4 days per week with fulvestrant versus placebo with fulvestrant. Random assignment was stratified by presence of liver metastases, previous treatment with CDK4\/6i, cyclin-dependent kinase four and six (CDK4\/6) inhibitors, and geographical region.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>A statistically significant progression-free survival (PFS) benefit was demonstrated in the overall population (hazard ratio [HR], 0.6 [95% CI, 0.51 to 0.71]); this result was driven by 289 patients in the biomarker-positive population (HR, 0.5 [95% CI, 0.37 to 0.68]). An exploratory analysis of investigator-assessed PFS in the 313 (44%) patients in the biomarker-negative population showed uncertain benefit (HR, 0.78 [95% CI, 0.60 to 1.01]). With capivasertib, more patients had Grade \u22653 toxicities. Key concerns included hyperglycemia (18% all-grade, 2.8% Grade \u22653), cutaneous toxicity (58% all-grade, 17% Grade \u22653), and diarrhea (72% all-grade, 9% Grade \u22653).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Capivasertib with fulvestrant was approved for patients whose tumors harbored\n                      <jats:italic>PIK3CA\/AKT1\/<\/jats:italic>\n                      <jats:italic>PTEN<\/jats:italic>\n                      alterations. Benefit-risk assessment in this subgroup was favorable based on a statistically significant and clinically meaningful improvement in PFS in the context of an acceptable safety profile including no evidence of a potential detriment in overall survival. By contrast, the benefit-risk was unfavorable in the biomarker-negative population.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.24.00427","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T15:59:18Z","timestamp":1724083158000},"page":"4103-4113","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":54,"title":["US Food and Drug Administration Approval Summary: Capivasertib With Fulvestrant for Hormone Receptor\u2013Positive, Human Epidermal Growth Factor Receptor 2\u2013Negative Locally Advanced or Metastatic Breast Cancer With\n                    <i>PIK3CA<\/i>\n                    \/\n                    <i>AKT1<\/i>\n                    \/\n                    <i>PTEN<\/i>\n                    Alterations"],"prefix":"10.1200","volume":"42","clinical-trial-number":[{"clinical-trial-number":"nct04305496","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5706-9138","authenticated-orcid":false,"given":"Asma","family":"Dilawari","sequence":"first","affiliation":[{"name":"Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Buturla","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy","family":"Osgood","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration, Silver Spring, 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