{"doi":"10.1200/jco.24.00427","title":"US Food and Drug Administration Approval Summary: Capivasertib With Fulvestrant for Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Locally Advanced or Metastatic Breast Cancer With <i>PIK3CA</i> / <i>AKT1</i> / <i>PTEN</i> Alterations","abstract":"PURPOSE The US Food and Drug Administration (FDA) approved capivasertib in combination with fulvestrant for adult patients with hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative, 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 ( PIK3CA )/AKT Serine/Threonine Kinase 1 ( AKT1 )/phosphatase and tensin homolog ( PTEN ) alterations, as detected by an FDA-approved test. PATIENTS AND METHODS Approval was based on CAPItello-291, a randomized, double-blind, multicenter trial of 708 patients with hormone receptor–positive, HER2-negative advanced or MBC, including 289 patients with PIK3CA/AKT1/PTEN 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. RESULTS 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 ≥3 toxicities. Key concerns included hyperglycemia (18% all-grade, 2.8% Grade ≥3), cutaneous toxicity (58% all-grade, 17% Grade ≥3), and diarrhea (72% all-grade, 9% Grade ≥3). CONCLUSION Capivasertib with fulvestrant was approved for patients whose tumors harbored PIK3CA/AKT1/ PTEN 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.","journal":"Journal of Clinical Oncology","year":2024,"id":419383,"datarank":0.9779689457864931,"base_score":3.7376696182833684,"endowment":3.7376696182833684,"self_citation_contribution":0.5606504427425053,"citation_network_contribution":0.4173185030439878,"self_endowment_contribution":0.5606504427425053,"citer_contribution":0.4173185030439878,"corpus_percentile":null,"corpus_rank":null,"citation_count":41,"citer_count":41,"citers_with_citation_signal":27,"citers_with_endowment":27,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9393,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT04305496"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1209328,"name":"James Buturla","orcid":null,"position":1,"is_corresponding":false},{"id":626322,"name":"Christy Osgood","orcid":"0000-0001-7450-9342","position":2,"is_corresponding":false},{"id":1208834,"name":"Xin Gao","orcid":"0000-0002-7383-6453","position":3,"is_corresponding":false},{"id":841966,"name":"Wei Chen","orcid":"0000-0003-3213-5412","position":4,"is_corresponding":false},{"id":256833,"name":"Tiffany K. Ricks","orcid":null,"position":5,"is_corresponding":false},{"id":1209329,"name":"Timothy J. Schaefer","orcid":null,"position":6,"is_corresponding":false},{"id":1209330,"name":"Sreedevi Avasarala","orcid":null,"position":7,"is_corresponding":false},{"id":256839,"name":"Francisca Reyes Turcu","orcid":null,"position":8,"is_corresponding":false},{"id":254107,"name":"Anand Pathak","orcid":"0000-0002-5707-5316","position":9,"is_corresponding":false},{"id":1020498,"name":"Shyam Kalavar","orcid":null,"position":10,"is_corresponding":false},{"id":1208835,"name":"Vishal Bhatnagar","orcid":"0000-0003-4650-0513","position":11,"is_corresponding":false},{"id":1039931,"name":"Justin S. Collazo","orcid":null,"position":12,"is_corresponding":false},{"id":866119,"name":"Nam Atiqur Rahman","orcid":"0009-0001-0002-7006","position":13,"is_corresponding":false},{"id":843766,"name":"Bronwyn D. Mixter","orcid":"0000-0001-5277-4399","position":14,"is_corresponding":false},{"id":254111,"name":"Shenghui Tang","orcid":"0000-0002-0437-665X","position":15,"is_corresponding":false},{"id":254114,"name":"Richard Pazdur","orcid":"0000-0002-4771-9923","position":16,"is_corresponding":false},{"id":234762,"name":"Paul G. Kluetz","orcid":"0000-0002-9796-4791","position":17,"is_corresponding":false},{"id":254112,"name":"Laleh Amiri‐Kordestani","orcid":"0000-0002-0056-5437","position":18,"is_corresponding":false},{"id":641924,"name":"Asma Dilawari","orcid":"0000-0001-5706-9138","position":0,"is_corresponding":true}],"reference_count":13,"raw_metadata":null,"created_at":"2026-07-19T01:57:14.586331Z","pmid":"39159418","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}