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Alpelisib for PIK3CA-mutated, hormone receptor–positive advanced breast cancer

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dc.contributor.authorAndré, Fabrice
dc.contributor.authorCiruelos, Eva
dc.contributor.authorRubovszky, Gabor
dc.contributor.authorCampone, Mario
dc.contributor.authorLoibl, Sibylle
dc.contributor.authorRugo, Hope S.
dc.contributor.authorIwata, Hiroji
dc.contributor.authorConte, Pierfranco
dc.contributor.authorMayer, Ingrid A.
dc.contributor.authorKaufman, Bella
dc.contributor.authorYamashita, Toshinari
dc.contributor.authorLu, Yen-Shen
dc.contributor.authorInoue, Kenichi
dc.contributor.authorTakahashi, Masato
dc.contributor.authorPápai, Zsuzsanna
dc.contributor.authorLongin, Anne-Sophie
dc.contributor.authorMills, David
dc.contributor.authorWilke, Celine
dc.contributor.authorHirawat, Samit
dc.contributor.authorJuric, Dejan
dc.contributor.authorAlonso Romero, José Luis
dc.contributor.departmentMedicina
dc.date.accessioned2024-11-07T09:37:20Z
dc.date.available2024-11-07T09:37:20Z
dc.date.issued2019-05-15
dc.description© 2019 Massachusetts Medical Society. All rights reserved. This document is the Published version of a Published Work that appeared in final form in New England Journal of Medicine.To access the final edited and published work see https://doi.org/10.1056/NEJMoa1813904
dc.description.abstractBackground: PIK3CA mutations occur in approximately 40% of patients with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer. The PI3Kα-specific inhibitor alpelisib has shown antitumor activity in early studies. Methods: In a randomized, phase 3 trial, we compared alpelisib (at a dose of 300 mg per day) plus fulvestrant (at a dose of 500 mg every 28 days and once on day 15) with placebo plus fulvestrant in patients with HR-positive, HER2-negative advanced breast cancer who had received endocrine therapy previously. Patients were enrolled into two cohorts on the basis of tumor-tissue PIK3CA mutation status. The primary end point was progression-free survival, as assessed by the investigator, in the cohort with PIK3CA-mutated cancer; progression-free survival was also analyzed in the cohort without PIK3CA-mutated cancer. Secondary end points included overall response and safety. Results: A total of 572 patients underwent randomization, including 341 patients with confirmed tumor-tissue PIK3CA mutations. In the cohort of patients with PIK3CA-mutated cancer, progression-free survival at a median follow-up of 20 months was 11.0 months (95% confidence interval [CI], 7.5 to 14.5) in the alpelisib–fulvestrant group, as compared with 5.7 months (95% CI, 3.7 to 7.4) in the placebo–fulvestrant group (hazard ratio for progression or death, 0.65; 95% CI, 0.50 to 0.85; P<0.001); in the cohort without PIK3CA-mutated cancer, the hazard ratio was 0.85 (95% CI, 0.58 to 1.25; posterior probability of hazard ratio <1.00, 79.4%). Overall response among all the patients in the cohort with PIK3CA-mutated cancer was greater with alpelisib–fulvestrant than with placebo–fulvestrant (26.6% vs. 12.8%); among patients with measurable disease in this cohort, the percentages were 35.7% and 16.2%, respectively. In the overall population, the most frequent adverse events of grade 3 or 4 were hyperglycemia (36.6% in the alpelisib–fulvestrant group vs. 0.7% in the placebo–fulvestrant group) and rash (9.9% vs. 0.3%). Diarrhea of grade 3 occurred in 6.7% of patients in the alpelisib–fulvestrant group, as compared with 0.3% of those in the placebo–fulvestrant group; no diarrhea of grade 4 was reported. The percentages of patients who discontinued alpelisib and placebo owing to adverse events were 25.0% and 4.2%, respectively. Conclusions: Treatment with alpelisib–fulvestrant prolonged progression-free survival among patients with PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer who had received endocrine therapy previously. (Funded by Novartis Pharmaceuticals; SOLAR-1 ClinicalTrials.gov number, NCT02437318.)es
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dc.format.extent12es
dc.identifier.citationN Engl J Med 2019 380:1929-1940
dc.identifier.doihttps://doi.org/10.1056/NEJMoa1813904
dc.identifier.issnPrint: 0028-4793
dc.identifier.issnElectronic: 1533-4406
dc.identifier.urihttp://hdl.handle.net/10201/146066
dc.languageenges
dc.publisherMassachusetts Medical Society
dc.relationSin financiación externa a la Universidades
dc.relation.publisherversionhttps://www.nejm.org/doi/10.1056/NEJMoa1813904
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccess
dc.titleAlpelisib for PIK3CA-mutated, hormone receptor–positive advanced breast canceres
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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