TY - JOUR
T1 - Phenotype-guided targeted therapy based on functional signal transduction pathway activity in recurrent ovarian cancer patients
T2 - The STAPOVER study protocol
AU - van der Ploeg, Phyllis
AU - Hendrikse, Cynthia SE
AU - Thijs, Anna MJ
AU - Westgeest, Hans M.
AU - Smedts, Huberdina PM
AU - Vos, M. Caroline
AU - Jalving, Mathilde
AU - Lok, Christianne AR
AU - Boere, Ingrid A.
AU - van Ham, Maaike APC
AU - Ottevanger, Petronella B.
AU - Westermann, Anneke M.
AU - Mom, Constantijne H.
AU - Lalisang, Roy I.
AU - Lambrechts, Sandrina
AU - Bekkers, Ruud LM
AU - Piek, Jurgen MJ
N1 - Funding Information:
This work is supported by the Catharina Research fund [grant number 2022–3] and InnoSIGN (previously Molecular Pathway Diagnostics, Philips ). Furthermore, this work is co-financed by the European Union through the subsidy program OPZUID (project number STIM-00107 ).
Publisher Copyright:
© 2023
PY - 2024/1/15
Y1 - 2024/1/15
N2 - Objective: Ovarian cancer is the fifth cause of cancer-related death among women. The benefit of targeted therapy for ovarian cancer patients is limited even if treatment is stratified by molecular signature. There remains a high unmet need for alternative diagnostics that better predict targeted therapy, as current diagnostics are generally inaccurate predictors. Quantitative assessment of functional signal transduction pathway (STP) activity from mRNA measurements of target genes is an alternative approach. Therefore, we aim to identify aberrantly activated STPs in tumour tissue of patients with recurrent ovarian cancer and start phenotype-guided targeted therapy to improve survival without compromising quality of life. Study design: Patients with recurrent ovarian cancer and either 1) have platinum-resistant disease, 2) refrain from standard therapy or 3) are asymptomatic and not yet eligible for standard therapy will be included in this multi-centre prospective cohort study with multiple stepwise executed treatment arms. Targeted therapy will be available for patients with aberrantly high functional activity of the oestrogen receptor, androgen receptor, phosphoinositide 3-kinase or Hedgehog STP. The primary endpoint of this study is the progression-free survival (PFS) ratio (PFS2/PFS1 ratio) according to RECIST 1.1 determined by the PFS on matched targeted therapy (PFS2) compared to PFS on prior therapy (PFS1). Secondary endpoints include among others best overall response, overall survival, side effects, health-related quality of life and cost-effectiveness. Conclusion: The results of this study will show the clinical applicability of STP activity in selecting recurrent ovarian cancer patients for effective therapies.
AB - Objective: Ovarian cancer is the fifth cause of cancer-related death among women. The benefit of targeted therapy for ovarian cancer patients is limited even if treatment is stratified by molecular signature. There remains a high unmet need for alternative diagnostics that better predict targeted therapy, as current diagnostics are generally inaccurate predictors. Quantitative assessment of functional signal transduction pathway (STP) activity from mRNA measurements of target genes is an alternative approach. Therefore, we aim to identify aberrantly activated STPs in tumour tissue of patients with recurrent ovarian cancer and start phenotype-guided targeted therapy to improve survival without compromising quality of life. Study design: Patients with recurrent ovarian cancer and either 1) have platinum-resistant disease, 2) refrain from standard therapy or 3) are asymptomatic and not yet eligible for standard therapy will be included in this multi-centre prospective cohort study with multiple stepwise executed treatment arms. Targeted therapy will be available for patients with aberrantly high functional activity of the oestrogen receptor, androgen receptor, phosphoinositide 3-kinase or Hedgehog STP. The primary endpoint of this study is the progression-free survival (PFS) ratio (PFS2/PFS1 ratio) according to RECIST 1.1 determined by the PFS on matched targeted therapy (PFS2) compared to PFS on prior therapy (PFS1). Secondary endpoints include among others best overall response, overall survival, side effects, health-related quality of life and cost-effectiveness. Conclusion: The results of this study will show the clinical applicability of STP activity in selecting recurrent ovarian cancer patients for effective therapies.
KW - Off-label drugs
KW - Ovarian cancer
KW - Signal transduction pathways
KW - Survival
KW - targeted therapy
U2 - 10.1016/j.heliyon.2023.e23170
DO - 10.1016/j.heliyon.2023.e23170
M3 - Article
SN - 2405-8440
VL - 10
JO - Heliyon
JF - Heliyon
IS - 1
M1 - e23170
ER -