{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T10:42:20Z","timestamp":1788172940166,"version":"build-2803163510"},"reference-count":40,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2023,5,1]]},"abstract":"<jats:sec><jats:title>Importance<\/jats:title><jats:p>Patients with platinum-resistant or refractory ovarian high-grade serous carcinoma (PR-HGSC) have a poor prognosis and few therapeutic options. Preclinical studies support targeting PI3K\/AKT\/mTOR signaling in this setting, and a phase 1 study of the dual mTORC1\/mTORC2 inhibitor vistusertib with weekly paclitaxel showed activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate whether the addition of vistusertib to weekly paclitaxel improves clinical outcomes in patients with PR-HGSC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This phase 2, double-blind, placebo-controlled multicenter randomized clinical trial recruited patients from UK cancer centers between January 2016 and March 2018. Patients with PR-HGSC of ovarian, fallopian tube, or primary peritoneal origin and with measurable or evaluable disease (Response Evaluation Criteria in Solid Tumors version 1.1 and\/or Gynecological Cancer Intergroup cancer antigen 125 criteria) were eligible. There were no restrictions on number of lines of prior therapy. Data analysis was performed from May 2019 to January 2022.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interventions<\/jats:title><jats:p>Patients were randomized (1:1) to weekly paclitaxel (80 mg\/m<jats:sup>2<\/jats:sup> days 1, 8, and 15 of a 28-day cycle) plus oral vistusertib (50 mg twice daily) or placebo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The primary end point was progression-free survival in the intention-to-treat population. Secondary end points included response rate, overall survival, and quality of life.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 140 patients (median [range] age, 63 [36-86] years; 17.9% with platinum-refractory disease; 53.6%\u2009with \u22653 prior therapies) were randomized. In the paclitaxel plus vistusertib vs paclitaxel plus placebo groups, there was no difference in progression-free survival (median, 4.5 vs 4.1 months; hazard ratio [HR], 0.84; 80% CI, 0.67-1.07; 1-sided <jats:italic>P<\/jats:italic>\u2009=\u2009.18), overall survival (median, 9.7 vs 11.1 months; HR, 1.21; 80% CI, 0.91-1.60) or response rate (odds ratio, 0.86; 80% CI, 0.55-1.36). Grade 3 to 4 adverse events were 41.2% (weekly paclitaxel plus vistusertib) vs 36.7% (weekly paclitaxel plus placebo), and there was no difference in quality of life.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Relevance<\/jats:title><jats:p>In this randomized clinical trial of weekly paclitaxel and dual mTORC1\/2 inhibition in patients with PR-HGSC, vistusertib did not improve clinical activity of weekly paclitaxel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>isrctn.org Identifier: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.isrctn.com\/ISRCTN16426935\">ISRCTN16426935<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaoncol.2022.7966","type":"journal-article","created":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T11:01:14Z","timestamp":1678964474000},"page":"675","source":"Crossref","is-referenced-by-count":27,"title":["Efficacy and Safety of Weekly Paclitaxel Plus Vistusertib vs Paclitaxel Alone in Patients With Platinum-Resistant Ovarian High-Grade Serous Carcinoma"],"prefix":"10.1001","volume":"9","author":[{"given":"Susana","family":"Banerjee","sequence":"first","affiliation":[{"name":"Gynaecology Unit, The Royal Marsden NHS Foundation Trust, London, United Kingdom"},{"name":"Division of Clinical Studies, Institute of Cancer Research, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia","family":"Giannone","sequence":"additional","affiliation":[{"name":"Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R.","family":"Clamp","sequence":"additional","affiliation":[{"name":"The Christie NHS Foundation Trust and University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren P.","family":"Ennis","sequence":"additional","affiliation":[{"name":"Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalind M.","family":"Glasspool","sequence":"additional","affiliation":[{"name":"Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Herbertson","sequence":"additional","affiliation":[{"name":"Sussex Cancer Centre, Royal Sussex County Hospital, Brighton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Krell","sequence":"additional","affiliation":[{"name":"Medical Oncology, Imperial College Healthcare NHS Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Riisnaes","sequence":"additional","affiliation":[{"name":"Division of Cancer Therapeutics, Institute of Cancer Research, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan B.","family":"Mirza","sequence":"additional","affiliation":[{"name":"Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Cheng","sequence":"additional","affiliation":[{"name":"Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"McDermott","sequence":"additional","affiliation":[{"name":"Department of Histopathology, Imperial College Healthcare NHS Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"Green","sequence":"additional","affiliation":[{"name":"University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca S.","family":"Kristeleit","sequence":"additional","affiliation":[{"name":"Research Department of Oncology, UCL Cancer Institute, University College London, London, United Kingdom"},{"name":"Now with Guy\u2019s and St Thomas\u2019 NHS Foundation Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"George","sequence":"additional","affiliation":[{"name":"Gynaecology Unit, The Royal Marsden NHS Foundation Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlie","family":"Gourley","sequence":"additional","affiliation":[{"name":"Cancer Research UK Scotland Centre, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liz-Anne","family":"Lewsley","sequence":"additional","affiliation":[{"name":"CRUK Glasgow Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie","family":"Rai","sequence":"additional","affiliation":[{"name":"CRUK Glasgow Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udai","family":"Banerji","sequence":"additional","affiliation":[{"name":"Division of Cancer Therapeutics, Institute of Cancer Research, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Hinsley","sequence":"additional","affiliation":[{"name":"CRUK Glasgow Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain A.","family":"McNeish","sequence":"additional","affiliation":[{"name":"Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, United Kingdom"},{"name":"Medical Oncology, Imperial College Healthcare NHS Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"10","key":"coi220103r1","doi-asserted-by":"publisher","first-page":"1988","DOI":"10.1093\/annonc\/mdu363","article-title":"A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer.","volume":"25","author":"McNeish","year":"2014","journal-title":"Ann Oncol"},{"issue":"3","key":"coi220103r2","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1016\/j.bbrc.2010.03.029","article-title":"Role of the Akt\/mTOR survival pathway in cisplatin resistance in ovarian cancer cells.","volume":"394","author":"Peng","year":"2010","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"coi220103r3","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.ygyno.2019.01.012","article-title":"A novel PI3K\/mTOR dual inhibitor, CMG002, overcomes the chemoresistance in ovarian cancer.","volume":"153","author":"Choi","year":"2019","journal-title":"Gynecol Oncol"},{"issue":"7","key":"coi220103r4","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1158\/1535-7163.MCT-11-0996","article-title":"The association of PI3 kinase signaling and chemoresistance in advanced ovarian cancer.","volume":"11","author":"Carden","year":"2012","journal-title":"Mol Cancer Ther"},{"issue":"69","key":"coi220103r5","doi-asserted-by":"publisher","first-page":"113874","DOI":"10.18632\/oncotarget.v8i69","article-title":"Evaluation of the combination of the dual m-TORC1\/2 inhibitor vistusertib (AZD2014) and paclitaxel in ovarian cancer models.","volume":"8","author":"Wong Te Fong","year":"2017","journal-title":"Oncotarget"},{"issue":"1","key":"coi220103r6","doi-asserted-by":"publisher","first-page":"6360","DOI":"10.1038\/s41467-022-33870-0","article-title":"Clonal somatic copy number altered driver events inform drug sensitivity in high-grade serous ovarian cancer.","volume":"13","author":"Martins","year":"2022","journal-title":"Nat Commun"},{"issue":"1","key":"coi220103r7","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.ygyno.2011.06.022","article-title":"Phase II trial of the mTOR inhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: a Gynecologic Oncology Group study.","volume":"123","author":"Behbakht","year":"2011","journal-title":"Gynecol Oncol"},{"issue":"9","key":"coi220103r8","doi-asserted-by":"publisher","first-page":"1918","DOI":"10.1093\/annonc\/mdy245","article-title":"Vistusertib (dual m-TORC1\/2 inhibitor) in combination with paclitaxel in patients with high-grade serous ovarian and squamous non-small-cell lung cancer.","volume":"29","author":"Basu","year":"2018","journal-title":"Ann Oncol"},{"issue":"2","key":"coi220103r9","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1097\/IGC.0b013e3182070f17","article-title":"Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG).","volume":"21","author":"Rustin","year":"2011","journal-title":"Int J Gynecol Cancer"},{"issue":"19","key":"coi220103r10","doi-asserted-by":"publisher","first-page":"3525","DOI":"10.1002\/(ISSN)1097-0258","article-title":"A three-outcome design for randomized comparative phase II clinical trials.","volume":"26","author":"Hong","year":"2007","journal-title":"Stat Med"},{"issue":"3","key":"coi220103r11","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.2307\/2531701","article-title":"Changing frequency of interim analysis in sequential monitoring.","volume":"45","author":"Lan","year":"1989","journal-title":"Biometrics"},{"issue":"4","key":"coi220103r12","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1177\/009286150103500408","article-title":"Interim monitoring of group sequential trials using spending functions for the type I and type II error probabilities.","volume":"35","author":"Pampallona","year":"2001","journal-title":"Drug Inf J"},{"issue":"3","key":"coi220103r13","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1007\/s11121-007-0070-9","article-title":"How many imputations are really needed? some practical clarifications of multiple imputation theory.","volume":"8","author":"Graham","year":"2007","journal-title":"Prev Sci"},{"issue":"12","key":"coi220103r14","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1186\/s13059-014-0526-8","article-title":"Combined image and genomic analysis of high-grade serous ovarian cancer reveals PTEN loss as a common driver event and prognostic classifier.","volume":"15","author":"Martins","year":"2014","journal-title":"Genome Biol"},{"issue":"9","key":"coi220103r15","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1038\/s41588-018-0179-8","article-title":"Copy number signatures and mutational processes in ovarian carcinoma.","volume":"50","author":"Macintyre","year":"2018","journal-title":"Nat Genet"},{"issue":"10271","key":"coi220103r16","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/S0140-6736(20)32554-X","article-title":"Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial.","volume":"397","author":"Lheureux","year":"2021","journal-title":"Lancet"},{"issue":"13","key":"coi220103r17","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1200\/JCO.2013.51.4489","article-title":"Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial.","volume":"32","author":"Pujade-Lauraine","year":"2014","journal-title":"J Clin Oncol"},{"issue":"32","key":"coi220103r18","doi-asserted-by":"publisher","first-page":"3836","DOI":"10.1200\/JCO.2015.63.1408","article-title":"Bevacizumab combined with weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan in platinum-resistant recurrent ovarian cancer: analysis by chemotherapy cohort of the randomized phase III AURELIA trial.","volume":"33","author":"Poveda","year":"2015","journal-title":"J Clin Oncol"},{"issue":"2","key":"coi220103r19","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.ygyno.2018.01.019","article-title":"Phase 2 study evaluating intermittent and continuous linsitinib and weekly paclitaxel in patients with recurrent platinum resistant ovarian epithelial cancer.","volume":"149","author":"Oza","year":"2018","journal-title":"Gynecol Oncol"},{"issue":"21","key":"coi220103r20","doi-asserted-by":"publisher","first-page":"2516","DOI":"10.1200\/JCO.2015.66.0787","article-title":"Double-blind, placebo-controlled, randomized phase III trial evaluating pertuzumab combined with chemotherapy for low tumor human epidermal growth factor receptor 3 mRNA-expressing platinum-resistant ovarian cancer (PENELOPE).","volume":"34","author":"Kurzeder","year":"2016","journal-title":"J Clin Oncol"},{"issue":"22","key":"coi220103r21","doi-asserted-by":"publisher","first-page":"5525","DOI":"10.1158\/1078-0432.CCR-18-0494","article-title":"Phase Ib study of binimetinib with paclitaxel in patients with platinum-resistant ovarian cancer: final results, potential biomarkers, and extreme responders.","volume":"24","author":"Grisham","year":"2018","journal-title":"Clin Cancer Res"},{"issue":"3","key":"coi220103r22","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.ygyno.2018.10.001","article-title":"A phase II evaluation of elesclomol sodium and weekly paclitaxel in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube or primary peritoneal cancer: an NRG Oncology\/Gynecologic Oncology Group study.","volume":"151","author":"Monk","year":"2018","journal-title":"Gynecol Oncol"},{"issue":"25","key":"coi220103r23","doi-asserted-by":"publisher","first-page":"2416","DOI":"10.1056\/NEJMoa1911361","article-title":"Olaparib plus bevacizumab as first-line maintenance in ovarian cancer.","volume":"381","author":"Ray-Coquard","year":"2019","journal-title":"N Engl J Med"},{"issue":"26","key":"coi220103r24","doi-asserted-by":"publisher","first-page":"2484","DOI":"10.1056\/NEJMoa1103799","article-title":"A phase 3 trial of bevacizumab in ovarian cancer.","volume":"365","author":"Perren","year":"2011","journal-title":"N Engl J Med"},{"issue":"26","key":"coi220103r25","doi-asserted-by":"publisher","first-page":"2473","DOI":"10.1056\/NEJMoa1104390","article-title":"Incorporation of bevacizumab in the primary treatment of ovarian cancer.","volume":"365","author":"Burger","year":"2011","journal-title":"N Engl J Med"},{"issue":"33","key":"coi220103r26","doi-asserted-by":"publisher","first-page":"5165","DOI":"10.1200\/JCO.2007.11.5345","article-title":"Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group study.","volume":"25","author":"Burger","year":"2007","journal-title":"J Clin Oncol"},{"issue":"33","key":"coi220103r27","doi-asserted-by":"publisher","first-page":"5180","DOI":"10.1200\/JCO.2007.12.0782","article-title":"Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer.","volume":"25","author":"Cannistra","year":"2007","journal-title":"J Clin Oncol"},{"issue":"7353","key":"coi220103r28","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1038\/nature10166","article-title":"Integrated genomic analyses of ovarian carcinoma.","volume":"474","author":"Cancer Genome Atlas Research Network","year":"2011","journal-title":"Nature"},{"issue":"7553","key":"coi220103r29","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1038\/nature14410","article-title":"Whole-genome characterization of chemoresistant ovarian cancer.","volume":"521","author":"Patch","year":"2015","journal-title":"Nature"},{"issue":"31","key":"coi220103r30","doi-asserted-by":"publisher","first-page":"3803","DOI":"10.1200\/JCO.2014.59.0018","article-title":"Inhibition of the PI3K\/AKT\/mTOR pathway in solid tumors.","volume":"34","author":"LoRusso","year":"2016","journal-title":"J Clin Oncol"},{"issue":"5","key":"coi220103r31","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1158\/1078-0432.CCR-18-2277","article-title":"Phase IB dose escalation and expansion study of AKT inhibitor afuresertib with carboplatin and paclitaxel in recurrent platinum-resistant ovarian cancer.","volume":"25","author":"Blagden","year":"2019","journal-title":"Clin Cancer Res"},{"issue":"1","key":"coi220103r32","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.ygyno.2016.04.019","article-title":"A randomized phase II non-comparative study of PF-04691502 and gedatolisib (PF-05212384) in patients with recurrent endometrial cancer.","volume":"142","author":"Del Campo","year":"2016","journal-title":"Gynecol Oncol"},{"issue":"4","key":"coi220103r33","doi-asserted-by":"publisher","first-page":"802","DOI":"10.3390\/cancers12040802","article-title":"ER and PI3K pathway activity in primary ER positive breast cancer is associated with progression-free survival of metastatic patients under first-line tamoxifen.","volume":"12","author":"Sieuwerts","year":"2020","journal-title":"Cancers (Basel)"},{"key":"coi220103r34","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.774103","article-title":"mTOR-mediated regulation of immune responses in cancer and tumor microenvironment.","volume":"12","author":"Mafi","year":"2022","journal-title":"Front Immunol"},{"issue":"5","key":"coi220103r35","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1038\/s41416-020-0900-0","article-title":"Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium.","volume":"123","author":"Martins","year":"2020","journal-title":"Br J Cancer"},{"issue":"10","key":"coi220103r37","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1038\/ng.2762","article-title":"Emerging landscape of oncogenic signatures across human cancers.","volume":"45","author":"Ciriello","year":"2013","journal-title":"Nat Genet"},{"issue":"13","key":"coi220103r38","doi-asserted-by":"publisher","first-page":"2911","DOI":"10.1158\/1078-0432.CCR-21-1643","article-title":"The genomic landscape of early-stage ovarian high-grade serous carcinoma.","volume":"28","author":"Cheng","year":"2022","journal-title":"Clin Cancer Res"},{"issue":"1","key":"coi220103r39","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/s41698-021-00187-y","article-title":"Integrated molecular characterisation of endometrioid ovarian carcinoma identifies opportunities for stratification.","volume":"5","author":"Hollis","year":"2021","journal-title":"NPJ Precis Oncol"},{"issue":"6","key":"coi220103r40","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1186\/s13058-014-0475-x","article-title":"Association of BRCA1\/2 defects with genomic scores predictive of DNA damage repair deficiency among breast cancer subtypes.","volume":"16","author":"Timms","year":"2014","journal-title":"Breast Cancer Res"},{"key":"coi220103r36","unstructured":"Dual mTorc inhibition in advanced\/recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer (of clear cell, endometrioid and high grade serous type, and carcinosarcoma) (DICE). ClinicalTrials.gov Identifier: NCT03648489. Updated March 11, 2022. Accessed February 10, 2023. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03648489"}],"container-title":["JAMA Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/articlepdf\/2802566\/jamaoncology_banerjee_2023_oi_220103_1686586761.94422.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T11:02:24Z","timestamp":1686826944000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/fullarticle\/2802566"}},"subtitle":["The OCTOPUS Multicenter, Phase 2, Randomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2023,5,1]]},"references-count":40,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,5,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaoncol.2022.7966","relation":{},"ISSN":["2374-2437"],"issn-type":[{"value":"2374-2437","type":"print"}],"subject":[],"published":{"date-parts":[[2023,5,1]]}}}