Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2021 Nov;163(2):433-444.
doi: 10.1016/j.ygyno.2021.07.008. Epub 2021 Jul 10.

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

Phyllis van der Ploeg  1 , Aniek Uittenboogaard  2 , Anna M J Thijs  3 , Hans M Westgeest  4 , Ingrid A Boere  5 , Sandrina Lambrechts  6 , Anja van de Stolpe  7 , Ruud L M Bekkers  8 , Jurgen M J Piek  2
Affiliations
Free article
Meta-Analysis

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

Phyllis van der Ploeg et al. Gynecol Oncol. 2021 Nov.
Free article

Abstract

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 <6 months as a beneficial outcome which resulted in a pooled CBR of 7% (95% CI 2-13%). The overall proportion of patients with drug-related grade 3 and 4 adverse events was 36%.

Conclusions: The efficacy of monotherapy with PI3K/AKT/mTOR inhibitors in advanced recurrent ovarian cancer patients is limited to a small subgroup and selection of patients with the use of current biomarkers did not improved the CBR significantly. Given the toxicity profile, we suggest that current treatment with PI3K/AKT/mTOR inhibitors should not be initiated unless in clinical trials. Furthermore, improved biomarkers to measure functional PI3K/AKT/mTOR pathway activity are needed to optimize patient selection.

Keywords: Akt; Mammalian target of rapamycin; Ovarian cancer; Phosphatidylinositol-3-kinase; Signal transduction pathway; Targeted therapy.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest PvdP is employed by Catharina Hospital, where her research work is co-funded by the Catharina research fund, and Molecular Pathway Dx, Philips. AvdS is employed by Molecular Pathway Dx, Philips. The other authors declare no conflict of interest.

Publication types

MeSH terms