Imperial College London
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DrJonathanKrell

Faculty of Medicine, Department of Surgery & Cancer

Clinical SL in Medical Oncology (Gynaecological Oncology)
 
 
 
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j.krell

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Banerjee:2023:10.1001/jamaoncol.2022.7966,
author = {Banerjee, S and Giannone, G and Clamp, AR and Ennis, DP and Glasspool, RM and Herbertson, R and Krell, J and Riisnaes, R and Mirza, HB and Cheng, Z and McDermott, J and Green, C and Kristeleit, RS and George, A and Gourley, C and Lewsley, L-A and Rai, D and Banerji, U and Hinsley, S and McNeish, IA},
doi = {10.1001/jamaoncol.2022.7966},
journal = {JAMA Oncology},
pages = {675--682},
title = {Efficacy and safety of weekly paclitaxel plus vistusertib vs paclitaxel alone in patients with platinum-resistant ovarian high-grade serous carcinoma: the octopus multicenter, phase 2, randomized clinical trial.},
url = {http://dx.doi.org/10.1001/jamaoncol.2022.7966},
volume = {9},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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/m2 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% (wee
AU  - Banerjee,S
AU  - Giannone,G
AU  - Clamp,AR
AU  - Ennis,DP
AU  - Glasspool,RM
AU  - Herbertson,R
AU  - Krell,J
AU  - Riisnaes,R
AU  - Mirza,HB
AU  - Cheng,Z
AU  - McDermott,J
AU  - Green,C
AU  - Kristeleit,RS
AU  - George,A
AU  - Gourley,C
AU  - Lewsley,L-A
AU  - Rai,D
AU  - Banerji,U
AU  - Hinsley,S
AU  - McNeish,IA
DO  - 10.1001/jamaoncol.2022.7966
EP  - 682
PY  - 2023///
SN  - 2374-2437
SP  - 675
TI  - Efficacy and safety of weekly paclitaxel plus vistusertib vs paclitaxel alone in patients with platinum-resistant ovarian high-grade serous carcinoma: the octopus multicenter, phase 2, randomized clinical trial.
T2  - JAMA Oncology
UR  - http://dx.doi.org/10.1001/jamaoncol.2022.7966
UR  - https://www.ncbi.nlm.nih.gov/pubmed/36928279
UR  - https://jamanetwork.com/journals/jamaoncology/fullarticle/2802566
UR  - http://hdl.handle.net/10044/1/102764
VL  - 9
ER  -
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