{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T10:02:24Z","timestamp":1784368944332,"version":"3.55.0"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T00:00:00Z","timestamp":1782518400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research and Development Program for Cancer Control, Ministry of Health and Welfare","award":["HA17C0054"],"award-info":[{"award-number":["HA17C0054"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This phase IB\/II study assessed safety, pharmacokinetics, and efficacy of alpelisib, a selective PI3K\u03b1 inhibitor, plus weekly paclitaxel in patients with PIK3CA-altered metastatic or recurrent gastric cancer (GC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In phase IB, patients with advanced solid tumors received alpelisib 250\u2009mg (dose level [DL] 0) or 300\u2009mg (DL1) once daily plus paclitaxel 70\u2009mg\/m2 on Days 1, 8, and 15 every 4\u2009weeks to determine maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended phase II dose (RP2D). In phase II, patients with PIK3CA-altered GC received RP2D, and the primary endpoint was 4-month progression-free survival (PFS). Subjects with diabetes or those with risk factors for diabetes who also had impaired glucose tolerance were excluded. Pharmacokinetic sampling was performed in phase IB at cycle 1, Days 1 (initial dose) and 8 (steady state).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In phase IB, MTD was not reached; RP2D was established at DL1. Two patients developed DLTs at DL0 (grade 3 hyperglycemia, diarrhea, and fatigue) and DL1 (grade 3 hyponatremia). Toxicities were consistent with known PI3K\u03b1 inhibitor plus taxane combination profiles and were generally manageable. In phase II (n\u2009=\u20099), the 4-month PFS rate was 22.2%, and enrollment was discontinued early for futility; no objective responses were observed, and the median PFS was 2.6\u2009months. Alpelisib exposure, assessed by Cmax and AUC0\u201324, was within expected ranges, and prior gastrectomy was associated with lower exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Alpelisib plus paclitaxel was tolerable and pharmacologically feasible with a defined RP2D but showed limited efficacy in PIK3CA-altered GC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag245","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T11:45:16Z","timestamp":1782387916000},"source":"Crossref","is-referenced-by-count":0,"title":["Phase IB\/II study of alpelisib combined with paclitaxel in patients with\n                    <i>PIK3CA<\/i>\n                    -altered metastatic or recurrent gastric cancer"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6426-9074","authenticated-orcid":false,"given":"Ji-Won","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine , Seongnam 13620,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seonghae","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics, Seoul National University Bundang Hospital, Seoul National University College of Medicine , Seongnam 13620,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Hee","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine , Seoul 05505,","place":["Republic of 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