{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:06:34Z","timestamp":1792785994947,"version":"4.5.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"the US National Institutes of Health to support the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai","award":["No. 5P30CA196521"],"award-info":[{"award-number":["No. 5P30CA196521"]}],"id":[{"id":"https:\/\/ror.org\/04a9tmd77","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The ASPIRE trial evaluated frontline anastrozole, palbociclib, trastuzumab, and pertuzumab in patients with hormone receptor\u2013positive, ERBB2 (formerly HER2 or HER2\/neu)-positive metastatic breast cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This phase 1\/2 trial enrolled patients with previously untreated hormone receptor\u2013positive, HER2-positive metastatic breast cancer. In phase 1, patients received escalating doses of palbociclib with trastuzumab, pertuzumab, and anastrozole, using a 3\u2009+\u20093 dose escalation design; the primary endpoint was maximum tolerated dose. Phase 2 followed an optimal Simon 2-stage design in which all patients received palbociclib at the maximum tolerated dose plus anastrozole, trastuzumab, and pertuzumab; the primary endpoint was clinical benefit rate in the first 6 months. Secondary endpoints included progression-free survival, overall survival, and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In phase 1, no dose-limiting toxicities were observed at the 100-mg (n\u2009=\u20093) or 125-mg (n\u2009=\u20096) dose levels; thus, 125\u2009mg was the maximum tolerated dose. An additional 23 patients were enrolled in phase 2, with a total of 29 patients in the response-evaluable population. The primary endpoint of clinical benefit rate was 97% (n\u2009=\u200928; 95% CI = 82% to 99%). At a median follow-up of 45.3\u2009months, median progression-free survival was 24.9\u2009months (95% CI = 17.2 to 44.8\u00a0months). Median overall survival was not reached at a follow-up of 39.4\u2009months. The most common treatment-related adverse events were neutropenia, leukopenia, diarrhea, and anemia. Grade 3 to 4 treatment-related adverse events occurred in 62% (n\u2009=\u200918) of patients, and most were hematological.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The combination of anastrozole, palbociclib, trastuzumab, and pertuzumab demonstrated promising activity in this single-arm trial of patients with hormone receptor\u2013positive, HER2-positive metastatic breast cancer and warrants further study in randomized trials. The regimen could provide a chemotherapy-free alternative.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djag256","type":"journal-article","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T11:40:38Z","timestamp":1784979638000},"source":"Crossref","is-referenced-by-count":0,"title":["A multicenter, phase 1\/2 trial of anastrozole, palbociclib, trastuzumab, and pertuzumab in hormone receptor\u2013positive, HER2-positive metastatic breast cancer (ASPIRE)"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3486-3085","authenticated-orcid":false,"given":"Rima","family":"Patel","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute , New York, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryann","family":"Kwa","sequence":"additional","affiliation":[{"name":"Department of 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