The effectiveness of monotherapy with PI3K/AKT/mTOR pathway inhibitors in ovarian cancer: A meta-analysis

Autor: Ruud L.M. Bekkers, Phyllis van der Ploeg, Sandrina Lambrechts, Jurgen M.J. Piek, Hans M. Westgeest, Anna M.J. Thijs, Aniek Uittenboogaard, Anja van de Stolpe, Ingrid A. Boere
Přispěvatelé: RS: GROW - R2 - Basic and Translational Cancer Biology, Obstetrie & Gynaecologie, MUMC+: MA Medische Staf Obstetrie Gynaecologie (9)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Oncology
medicine.medical_treatment
MULTICENTER
Targeted therapy
Phosphatidylinositol 3-Kinases
Clinical endpoint
1ST-IN-HUMAN
Phosphoinositide-3 Kinase Inhibitors
Ovarian Neoplasms
Mammalian target of rapamycin
PI3K PATHWAY
TOR Serine-Threonine Kinases
MTOR
Obstetrics and Gynecology
MTOR Inhibitors
Signal transduction pathway
Temsirolimus
Treatment Outcome
PHASE-I
ADVANCED SOLID TUMORS
Biomarker (medicine)
Female
TRIAL
medicine.drug
Signal Transduction
EPITHELIAL OVARIAN
medicine.medical_specialty
Clinical Decision-Making
Antineoplastic Agents
SDG 3 - Good Health and Well-being
Predictive Value of Tests
Ovarian cancer
Internal medicine
medicine
Biomarkers
Tumor
Humans
DOSE-ESCALATION
Protein kinase B
PI3K/AKT/mTOR pathway
Neoplasm Staging
business.industry
Patient Selection
Akt
medicine.disease
Clinical trial
Phosphatidylinositol-3-kinase
TEMSIROLIMUS
business
Proto-Oncogene Proteins c-akt
Zdroj: Gynecologic Oncology, 163(2), 433-444. Elsevier Science
ISSN: 1095-6859
0090-8258
DOI: 10.1016/j.ygyno.2021.07.008
Popis: Objective. To determine the clinical benefit of monotherapy with PI3K/AKT/mTOR inhibitors in patients diagnosed with advanced or recurrent ovarian cancer and to investigate the predictive value of current PI3K/AKT/ mTOR biomarkers on therapy response. Methods. A systematic search was conducted in PubMed, Embase and the Cochrane Library for articles reporting on treatment with PI3K/AKT/mTOR inhibitors in ovarian cancer. The primary endpoint was defined as the clinical benefit rate (CBR), including the proportion of patients with complete (CR) and partial response (PR) and stable disease (SD). Secondary endpoints included the overall response rate (ORR, including CR and PR) and drug-related grade 3 and 4 adverse events. Results. We included 233 patients from 19 studies and observed a pooled CBR of 32% (95% CI 20-44%) and ORR of 3% (95% CI 0-6%) in advanced or recurrent ovarian cancer patients treated with PI3K/AKT/mTOR inhibitors. Subgroup analysis tended to favor the studies who selected patients based on current PI3K/AKT/mTOR biomarker criteria (e.g. genomic alterations or loss of PTEN protein expression), but the difference in CBR was not statistically significant from studies with unselected populations (respectively, CBR of 42% (95% CI 23-62%) and 27% (95% CI 14-42%), P = 0.217). To better reflect true patient benefit, we excluded SD
Databáze: OpenAIRE
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