{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T05:25:55Z","timestamp":1794288355430,"version":"4.9.0"},"reference-count":28,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      The National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) (EAY131, ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT02465060\">NCT02465060<\/jats:ext-link>\n                      ) trial pairs patients with targeted therapies on the basis of tumor genomic alterations. Subprotocol T assessed vismodegib, a hedgehog pathway inhibitor, in patients with Patched-1 (\n                      <jats:italic toggle=\"yes\">PTCH1<\/jats:italic>\n                      ) and Smoothened (\n                      <jats:italic toggle=\"yes\">SMO<\/jats:italic>\n                      ) alterations (excluding basal cell carcinoma).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Eligible patients received oral vismodegib (150 mg daily) until progression or toxicity. The primary end point was objective response rate, with secondary end points including 6-month progression-free survival (PFS), survival, and predictive biomarkers. Optional plasma for cell-free DNA analysis was collected at enrollment, on treatment, and at progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      From June 2016 to September 2020, 34 patients enrolled; 31 eligible patients (nine\n                      <jats:italic toggle=\"yes\">SMO<\/jats:italic>\n                      , 22\n                      <jats:italic toggle=\"yes\">PTCH1<\/jats:italic>\n                      ) received treatment, with 25 confirmed by the central NCI-MATCH assay (primary analysis cohort). Median age of the 31 eligible patients was 64 years, with 48.4% being women. Sixty-one percent received \u22653 previous therapies and 74% had multiple co-occurring mutations. Objective response rate was 8% (2\/25 [90% CI, 1.4 to 23.1]) in the primary analysis cohort and 6.5% (2\/31 [90% CI, 1.2 to 19]) overall. Partial responses occurred in soft tissue sarcoma (\n                      <jats:italic toggle=\"yes\">PTCH1<\/jats:italic>\n                      ) and meningioma (\n                      <jats:italic toggle=\"yes\">SMO<\/jats:italic>\n                      ), with response durations of 19 and 9.23 months, respectively. Six-month PFS rates were similar (24%, 23.2%), with an identical median PFS of 1.8 months and median overall survival of 7.3 months for the analyzable and primary analysis patient cohorts. Four patients (12.9%) discontinued therapy because of adverse events. Common toxicities included grade 1-2 fatigue, anorexia, weight loss, alopecia, and dysgeusia. Four on-study deaths occurred, none treatment-related.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Vismodegib was well tolerated with mainly grade 1-2 toxicities, but it did not meet the primary end point. Select patients with specific\n                      <jats:italic toggle=\"yes\">SMO<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">PTCH1<\/jats:italic>\n                      alterations had notable responses, warranting further comprehensive molecular analyses to elucidate resistance mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-00119","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T19:59:10Z","timestamp":1760039950000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Phase II Study of Vismodegib in Patients With\n                    <i>SMO-<\/i>\n                    or\n                    <i>PTCH1<\/i>\n                    -Mutated Tumors: Results From the National Cancer Institute Molecular Analysis for Therapy Choice Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Trial (EAY131) Subprotocol T"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0505-6639","authenticated-orcid":true,"given":"Anne S.","family":"Tsao","sequence":"first","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihe","family":"Song","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute-ECOG-ACRIN Biostatistics Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6885-3742","authenticated-orcid":true,"given":"Alan L.","family":"Ho","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9492-9264","authenticated-orcid":true,"given":"Janice M.","family":"Mehnert","sequence":"additional","affiliation":[{"name":"Laura and Issac Perlmutter Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Percy","family":"Ivy","sequence":"additional","affiliation":[{"name":"Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5724-4917","authenticated-orcid":true,"given":"Robert J.","family":"Gray","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute-ECOG-ACRIN Biostatistics Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Wang","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute-ECOG-ACRIN Biostatistics Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8195-3206","authenticated-orcid":true,"given":"Lisa M.","family":"McShane","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute-ECOG-ACRIN Biostatistics Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9720-9737","authenticated-orcid":true,"given":"Larry V.","family":"Rubinstein","sequence":"additional","affiliation":[{"name":"Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3855-0166","authenticated-orcid":true,"given":"David R.","family":"Patton","sequence":"additional","affiliation":[{"name":"Center for Biomedical Informatics &amp; Information Technology, National Cancer Institute, Rockville, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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