{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:33:49Z","timestamp":1792805629920,"version":"4.5.0"},"reference-count":16,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"28","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>\n              The US Food and Drug Administration (FDA) approved inavolisib with palbociclib and fulvestrant for adults with endocrine-resistant,\n              <jats:italic toggle=\"yes\">PIK3CA<\/jats:italic>\n              -mutated, hormone receptor\u2013positive, human epidermal growth factor receptor 2 (HER2)\u2013negative, locally advanced or metastatic breast cancer (MBC), as detected by an FDA-approved test, FoundationOne Liquid CDx assay, after recurrence on or after completing adjuvant endocrine therapy.\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 INAVO120, a randomized, double-blind, placebo-controlled trial in 325 patients with endocrine-resistant,\n              <jats:italic toggle=\"yes\">PIK3CA<\/jats:italic>\n              -mutated, hormone receptor\u2013positive, HER2-negative, locally advanced or MBC. Patients were randomly assigned (1:1) to either inavolisib (n = 161) or placebo (n = 164) in combination with palbociclib and fulvestrant.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              INAVO120 met its primary end point of progression-free survival (PFS) by investigator assessment, with a median PFS of 15.0 months for inavolisib + palbociclib + fulvestrant versus 7.3 months for placebo + palbociclib + fulvestrant (hazard ratio [HR], 0.43 [95% CI, 0.32 to 0.59];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt; .0001). The objective response rate was 58% (95% CI, 50 to 66) versus 25% (95% CI, 19 to 32). The median duration of response was 18.4 months (95% CI, 10.4 to 22.2) versus 9.6 months (95% CI, 7.4 to 16.6). Interim analysis of overall survival did not reach statistical significance but was supportive of the overall benefit-risk assessment with a HR of 0.64 (95% CI, 0.43 to 0.97). Consistent with the PI3K\u03b1 inhibitor class, common adverse reactions noted with inavolisib included hyperglycemia, stomatitis, diarrhea, and rash.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>The approval of inavolisib with palbociclib plus fulvestrant was based on a statistically significant and clinically meaningful improvement in PFS observed in the INAVO120 trial. Before this approval, there were no specific therapies approved by the FDA for the first-line treatment of patients with endocrine-resistant, hormone receptor\u2013positive advanced or MBC.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/jco-25-00663","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T19:59:27Z","timestamp":1755892767000},"page":"3123-3131","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":12,"title":["US Food and Drug Administration Approval Summary: Inavolisib With Palbociclib and Fulvestrant for Endocrine-Resistant,\n            <i>PIK3CA<\/i>\n            -Mutated, Hormone Receptor\u2013Positive, Human Epidermal Growth Factor Receptor 2\u2013Negative, Locally Advanced or Metastatic Breast Cancer"],"prefix":"10.1200","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0455-5399","authenticated-orcid":true,"given":"Suparna","family":"Wedam","sequence":"first","affiliation":[{"name":"Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0825-9087","authenticated-orcid":true,"given":"Preeti","family":"Narayan","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6976-8777","authenticated-orcid":true,"given":"Haley","family":"Gittleman","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, 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