{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:47:56Z","timestamp":1788432476776,"version":"build-2803163510"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,12,30]],"date-time":"2019-12-30T00:00:00Z","timestamp":1577664000000},"content-version":"vor","delay-in-days":29,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA016672"],"award-info":[{"award-number":["P30CA016672"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Hematol Oncol"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>In 2007, we initiated IMPACT, a precision medicine program for patients referred for participation in early-phase clinical trials. We assessed the correlation of factors, including genomically matched therapy, with overall survival (OS).<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Patients and methods<\/jats:title>\n<jats:p>We performed molecular profiling (Clinical Laboratory Improvement Amendments) (genes \u2264\u2009182) for patients with lethal\/refractory advanced cancers referred to the Phase 1 Clinical Trials Program. Matched therapy, if available, was selected on the basis of genomics. Clinical trials varied over time and included investigational drugs against various targets (single agents or combinations). Patients were followed up for up to 10\u2009years.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Of 3487 patients who underwent tumor molecular profiling, 1307 (37.5%) had \u2265\u20091 alteration and received therapy (matched, 711; unmatched, 596; median age, 57\u2009years; 39% men). Most common tumors were gastrointestinal, gynecologic, breast, melanoma, and lung. Objective response rates were: matched 16.4%, unmatched 5.4% (<jats:italic>p<\/jats:italic> &lt; .0001); objective response plus\u00a0stable disease \u2265\u20096 months rates were:\u00a0matched\u00a035.3% and\u00a0unmatched 20.3%, (<jats:italic>p<\/jats:italic> &lt; .001). Respective median progression-free survival: 4.0 and 2.8\u2009months (<jats:italic>p<\/jats:italic> &lt; .0001); OS, 9.3 and 7.3\u2009months; 3-year, 15% versus 7%; 10-year, 6% vs. 1% (<jats:italic>p<\/jats:italic> &lt; .0001). Independent factors associated with shorter OS (multivariate analysis) were performance status &gt;\u20091 (<jats:italic>p<\/jats:italic> &lt; .001), liver metastases (<jats:italic>p<\/jats:italic> &lt; .001), lactate dehydrogenase levels &gt; upper limit of normal (<jats:italic>p<\/jats:italic> &lt; .001), PI3K\/AKT\/mTOR pathway alterations (<jats:italic>p<\/jats:italic> &lt; .001), and non-matched therapy (<jats:italic>p<\/jats:italic> &lt; .001). The five independent factors predicting shorter OS were used to design a prognostic score.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Matched targeted therapy was an independent factor predicting longer OS. A score to predict an individual patient\u2019s risk of death is proposed.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Trial registration<\/jats:title>\n<jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00851032\">NCT00851032<\/jats:ext-link>, date of registration February 25, 2009.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s13045-019-0835-1","type":"journal-article","created":{"date-parts":[[2019,12,30]],"date-time":"2019-12-30T22:02:51Z","timestamp":1577743371000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Long-term overall survival and prognostic score predicting survival: the IMPACT study in precision medicine"],"prefix":"10.1186","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2713-233X","authenticated-orcid":false,"given":"Apostolia-Maria","family":"Tsimberidou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer J.","family":"Wheler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald S.","family":"Falchook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Janku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aung","family":"Naing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqing","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarina","family":"Piha-Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie","family":"Cartwright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell R.","family":"Broaddus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graciela M.","family":"Nogueras Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Hwu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razelle","family":"Kurzrock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,30]]},"reference":[{"issue":"1","key":"835_CR1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s00439-011-1028-3","volume":"130","author":"K Offit","year":"2011","unstructured":"Offit K. 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Curr Probl Cancer. 2017;41(3):176\u201381.","journal-title":"Curr Probl Cancer."}],"container-title":["Journal of Hematology &amp; Oncology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13045-019-0835-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13045-019-0835-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13045-019-0835-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,29]],"date-time":"2020-12-29T00:31:33Z","timestamp":1609201893000},"score":1,"resource":{"primary":{"URL":"https:\/\/jhoonline.biomedcentral.com\/articles\/10.1186\/s13045-019-0835-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["835"],"URL":"https:\/\/doi.org\/10.1186\/s13045-019-0835-1","relation":{},"ISSN":["1756-8722"],"issn-type":[{"value":"1756-8722","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12]]},"assertion":[{"value":"28 August 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 December 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was approved by the MD Anderson Cancer Center Institutional Review Board. The trial was registered at  (NCT00851032).All patients provided written informed consent stating that they were aware of the experimental nature of the specific phase I study in which they participated. Clinical trials and analyses were conducted with the approval of and in accordance with the guidelines of the MD Anderson Cancer Center Institutional Review Board.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Apostolia-Maria Tsimberidou\u2014Research Funding: IMMATICS, Parker Institute for Cancer Immunotherapy, Tempus, EMD Serono; Baxalta; Foundation Medicine; ONYX; Bayer; Boston Biomedical; Placon Therapeutics; Karus Therapeutics; Tvardi; OBI Pharma. Consulting or Advisory Role: Roche, Covance, Genentech.David S Hong\u2014Research Funding: Adaptimmune, Abbvie, Amgen, AstraZeneca, Bayer, BMS, Daiichi-Sanko, Eisai, Genentech, Genmab, Ignyta, Infinity, Kite Kyowa, Lilly, LOXO, Mirati, Merck, Medimmune, Molecular Template, Novartis, Pfizer, Takeda. Travel, Accommodations, Expenses: LOXO, MiRNA. Consulting or Advisory Role: Baxter, Bayer, Guidepoint Global, Janssen, Genentech, Takeda. Other ownership interests: Molecular Match (Advisor), Oncoresponse (founder).Jennifer J Wheler\u2014Current employee of TScan Therapeutics. Stock owner in TScan Therapeutics.Gerald S. Falchook\u2014Research Funding: Millennium, EMD Serono, Celgene, MedImmune, Genmab, Vegenics, Novartis, AstraZeneca, Incyte, ARMO BioSciences, KollTan Pharmaceuticals, 3-V Biosciences, Abbvie, Aileron Therapeutics, DeMar Pharmaceuticals, eFFECTOR Therapeutics, Strategia Therapeutics, FujiFilm, Hutchison MediPharma, Regeneron, Biothera, Curegenix, Curis, Lilly, Jounce Therapeutics, OncoMed, Precision Oncology, Syndax, Taiho Pharmaceuticals, Tesaro, Takeda, BeiGene, Ignyta, Merck, Rgenix, Tarveda Therapeutics, Tocagen, Loxo. Royalties: Handbook of Targeted Cancer Therapy. Travel, Accommodations, Expenses: Millennium, Sarah Cannon Research Institute, EMD Serono, Bristol-Myers Squibb.Filip Janku\u2014Research Funding: Novartis, FujiFilm Pharmaceuticals, Plexxikon, Deciphera Pharmaceuticals, Symphogen, Asana, BioMed Valley Discoveries, Bristol-Myers Squibb, Genentech, Astellas Pharma, Agios, Pl QUR Therapeutics AG, Bayer, and Proximagen. Consulting Role: Deciphera Pharmaceuticals, Novartis, Synlogic, IFM Therapeutics, lllumina, GRAIL. Valeant, Sotio, Pure Tech Health, Guardant Health Trovagene, and lmmunoMet. Ownership interest in Trovagene.Aung Naing\u2014Research Funding: NCI; EMD Serono; MedImmune; Healios Onc. Nutrition; Atterocor; Amplimmune; ARMO BioSciences; Karyopharm Therapeutics; Incyte; Novartis; Regeneron; Merck; BMS; Pfizer; CytomX Therapeutics; Neon Therapeutics; Calithera Biosciences; TopAlliance Biosciences; Immune Deficiency Foundation (Spouse). Advisory board: CytomX Therapeutics and Novartis. Travel and accommodation expense from ARMO Biosciences.Siqing Fu\u2014Research Funding: Anaeropharma Science, Inc.; Aprea AB; AstraZeneca; Eli Lilly and Company; Endocyte; Ignyta; Millennium; NCCI; Novartis; OncoMed Pharmaceuticals, Inc.; Vertex Pharmaceuticals; Hengrui. Travel and Accommodations: Hebei Medical University, EMD Serono.Sarina Piha-Paul\u2014Research Funding: AbbVie, Inc.; Aminex Therapeutics; Bristol Myers Squibb; Curis, Inc.; Five Prime Therapeutics; GlaxoSmithKline; Helix BioPharma Corp.; Incyte, Inc.; MedImmune; Medivation, Inc.; Merck Sharp and Dohme; Novartis; Pieris; Pfizer; Principia Biopharma, Inc.; Puma Biotechnology, Inc.; Seattle Genetics; Taiho; Tesaro; TransThera Bio; XuanZhu Biopharma.Patrick Hwu\u2014Advisory role: Immatics, Dragonfly, Sanofi, GlaxoSmithKline.Razelle Kurzrock\u2014Research Funding: Incyte, Genentech, Merck Serono, Pfizer, Sequenom, Foundation Medicine, Guardant Health, Konica Minolta, Boehringer Ingelheim, and Debiopharm. Consultant fees: LOXO, X-Biotech, Actuate Therapeutics, Roche, Soluventis and NeoMed. Speaker fees: Roche. Ownership interest: CureMatch, Inc. Stock owner: IDbyDNA.The other authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"145"}}