Matches in SemOpenAlex for { <https://semopenalex.org/work/W4327578003> ?p ?o ?g. }
- W4327578003 endingPage "675" @default.
- W4327578003 startingPage "675" @default.
- W4327578003 abstract "Importance 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. Objective To evaluate whether the addition of vistusertib to weekly paclitaxel improves clinical outcomes in patients with PR-HGSC. Design, Setting, and Participants 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. Interventions Patients were randomized (1:1) to weekly paclitaxel (80 mg/m 2 days 1, 8, and 15 of a 28-day cycle) plus oral vistusertib (50 mg twice daily) or placebo. Main Outcomes and Measures 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. Results A total of 140 patients (median [range] age, 63 [36-86] years; 17.9% with platinum-refractory disease; 53.6% with ≥3 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 P = .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. Conclusions and Relevance 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. Trial Registration isrctn.org Identifier: ISRCTN16426935" @default.
- W4327578003 created "2023-03-17" @default.
- W4327578003 creator A5002216866 @default.
- W4327578003 creator A5003877775 @default.
- W4327578003 creator A5007279195 @default.
- W4327578003 creator A5007424793 @default.
- W4327578003 creator A5009351129 @default.
- W4327578003 creator A5014542203 @default.
- W4327578003 creator A5015356443 @default.
- W4327578003 creator A5032401979 @default.
- W4327578003 creator A5032801379 @default.
- W4327578003 creator A5040195796 @default.
- W4327578003 creator A5065447416 @default.
- W4327578003 creator A5066136399 @default.
- W4327578003 creator A5068598854 @default.
- W4327578003 creator A5076906881 @default.
- W4327578003 creator A5078730275 @default.
- W4327578003 creator A5080241438 @default.
- W4327578003 creator A5081724683 @default.
- W4327578003 creator A5084388857 @default.
- W4327578003 creator A5088144652 @default.
- W4327578003 creator A5089425681 @default.
- W4327578003 date "2023-05-01" @default.
- W4327578003 modified "2023-10-03" @default.
- W4327578003 title "Efficacy and Safety of Weekly Paclitaxel Plus Vistusertib vs Paclitaxel Alone in Patients With Platinum-Resistant Ovarian High-Grade Serous Carcinoma" @default.
- W4327578003 cites W1781764024 @default.
- W4327578003 cites W1996193504 @default.
- W4327578003 cites W2002710053 @default.
- W4327578003 cites W2026876171 @default.
- W4327578003 cites W2088845519 @default.
- W4327578003 cites W2096521047 @default.
- W4327578003 cites W2105651363 @default.
- W4327578003 cites W2107223717 @default.
- W4327578003 cites W2108643617 @default.
- W4327578003 cites W2109772731 @default.
- W4327578003 cites W2113122060 @default.
- W4327578003 cites W2123696077 @default.
- W4327578003 cites W2125898467 @default.
- W4327578003 cites W2130659669 @default.
- W4327578003 cites W2133494987 @default.
- W4327578003 cites W2135947389 @default.
- W4327578003 cites W2155341026 @default.
- W4327578003 cites W2166768348 @default.
- W4327578003 cites W2170928115 @default.
- W4327578003 cites W2326021992 @default.
- W4327578003 cites W2342880723 @default.
- W4327578003 cites W2416660942 @default.
- W4327578003 cites W2518718875 @default.
- W4327578003 cites W2775545562 @default.
- W4327578003 cites W2787266690 @default.
- W4327578003 cites W2805386901 @default.
- W4327578003 cites W2888480300 @default.
- W4327578003 cites W2896925652 @default.
- W4327578003 cites W2903881613 @default.
- W4327578003 cites W2911528643 @default.
- W4327578003 cites W2953270703 @default.
- W4327578003 cites W2994977341 @default.
- W4327578003 cites W3013664357 @default.
- W4327578003 cites W3036702906 @default.
- W4327578003 cites W3122624214 @default.
- W4327578003 cites W3165192994 @default.
- W4327578003 cites W4205753137 @default.
- W4327578003 cites W4213121631 @default.
- W4327578003 cites W4225526137 @default.
- W4327578003 cites W4246835333 @default.
- W4327578003 cites W4249999102 @default.
- W4327578003 cites W4307658814 @default.
- W4327578003 doi "https://doi.org/10.1001/jamaoncol.2022.7966" @default.
- W4327578003 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36928279" @default.
- W4327578003 hasPublicationYear "2023" @default.
- W4327578003 type Work @default.
- W4327578003 citedByCount "6" @default.
- W4327578003 countsByYear W43275780032023 @default.
- W4327578003 crossrefType "journal-article" @default.
- W4327578003 hasAuthorship W4327578003A5002216866 @default.
- W4327578003 hasAuthorship W4327578003A5003877775 @default.
- W4327578003 hasAuthorship W4327578003A5007279195 @default.
- W4327578003 hasAuthorship W4327578003A5007424793 @default.
- W4327578003 hasAuthorship W4327578003A5009351129 @default.
- W4327578003 hasAuthorship W4327578003A5014542203 @default.
- W4327578003 hasAuthorship W4327578003A5015356443 @default.
- W4327578003 hasAuthorship W4327578003A5032401979 @default.
- W4327578003 hasAuthorship W4327578003A5032801379 @default.
- W4327578003 hasAuthorship W4327578003A5040195796 @default.
- W4327578003 hasAuthorship W4327578003A5065447416 @default.
- W4327578003 hasAuthorship W4327578003A5066136399 @default.
- W4327578003 hasAuthorship W4327578003A5068598854 @default.
- W4327578003 hasAuthorship W4327578003A5076906881 @default.
- W4327578003 hasAuthorship W4327578003A5078730275 @default.
- W4327578003 hasAuthorship W4327578003A5080241438 @default.
- W4327578003 hasAuthorship W4327578003A5081724683 @default.
- W4327578003 hasAuthorship W4327578003A5084388857 @default.
- W4327578003 hasAuthorship W4327578003A5088144652 @default.
- W4327578003 hasAuthorship W4327578003A5089425681 @default.
- W4327578003 hasConcept C121608353 @default.
- W4327578003 hasConcept C126322002 @default.
- W4327578003 hasConcept C142724271 @default.
- W4327578003 hasConcept C143998085 @default.