TY - JOUR
T1 - Survival and modelled cancer antigen-125 ELIMination rate constant K score in ovarian cancer patients in first-line before poly(ADP-ribose) polymerase inhibitor era
T2 - A Gynaecologic Cancer Intergroup meta-analysis
AU - Corbaux, Pauline
AU - You, Benoit
AU - Glasspool, Rosalind M
AU - Yanaihara, Nozomu
AU - Tinker, Anna V
AU - Lindemann, Kristina
AU - Ray-Coquard, Isabelle L
AU - Mirza, Mansoor R
AU - Subtil, Fabien
AU - Colomban, Olivier
AU - Péron, Julien
AU - Karamouza, Eleni
AU - McNeish, Iain
AU - Kelly, Caroline
AU - Kagimura, Tatsuo
AU - Welch, Stephen
AU - Lewsley, Liz-Anne
AU - Paoletti, Xavier
AU - Cook, Adrian
N1 - Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
PY - 2023
Y1 - 2023
N2 - BACKGROUND: In patients with advanced ovarian cancer, the modelled CA-125 ELIMination rate constant K (KELIM) is an early indicator of the tumour intrinsic chemosensitivity. We assessed the prognostic and surrogate values of KELIM with respect to those of surgery outcome (based on post-operative residual lesions) in the Gynaecologic Cancer Intergroup (GCIG) individual patient data meta-analysis MAOV (Meta-Analysis in OVarian cancer) built before the emergence of poly(ADP-ribose) polymerase (PARP) inhibitors.METHODS: The dataset was split into learning and validation cohorts (ratio 1:2). The individual modelled KELIM values were estimated, standardised by the median value, then scored as unfavourable (<1.0) or favourable (≥1.0). Overall survival (OS) and progression-free survival (PFS) analyses were performed with a two-step meta-analytic approach and surrogacy through a two-level meta-analytic model.RESULTS: KELIM was assessed in 5884 patients from eight first-line trials (learning, 1962; validation, 3922). A favourable KELIM score was significantly associated with longer OS (validation set, median, 78.8 versus 28.4 months, hazard-ratios [HR] 0.46, 95% confidence interval [CI], 0.41-0.50, C-index 0.68), and longer PFS (validation set, median 30.5 versus 9.8 months, HR 0.49, 95% CI, 0.45-0.54, C-index 0.68), as were International Federation of Gynaecology and Obstetrics (FIGO) stage and debulking surgery outcome. Three prognostic groups were identified based on the surgery outcome and KELIM score, with large differences in OS (105.1, ∼45.0, and 22.1 months) and PFS (58.1, ∼15.0, and 8.0 months). Surrogacy for OS and for PFS was not established.CONCLUSION: KELIM is an independent prognostic biomarker for survival, complementary to surgery outcome, representing a new determinant of first-line treatment success.
AB - BACKGROUND: In patients with advanced ovarian cancer, the modelled CA-125 ELIMination rate constant K (KELIM) is an early indicator of the tumour intrinsic chemosensitivity. We assessed the prognostic and surrogate values of KELIM with respect to those of surgery outcome (based on post-operative residual lesions) in the Gynaecologic Cancer Intergroup (GCIG) individual patient data meta-analysis MAOV (Meta-Analysis in OVarian cancer) built before the emergence of poly(ADP-ribose) polymerase (PARP) inhibitors.METHODS: The dataset was split into learning and validation cohorts (ratio 1:2). The individual modelled KELIM values were estimated, standardised by the median value, then scored as unfavourable (<1.0) or favourable (≥1.0). Overall survival (OS) and progression-free survival (PFS) analyses were performed with a two-step meta-analytic approach and surrogacy through a two-level meta-analytic model.RESULTS: KELIM was assessed in 5884 patients from eight first-line trials (learning, 1962; validation, 3922). A favourable KELIM score was significantly associated with longer OS (validation set, median, 78.8 versus 28.4 months, hazard-ratios [HR] 0.46, 95% confidence interval [CI], 0.41-0.50, C-index 0.68), and longer PFS (validation set, median 30.5 versus 9.8 months, HR 0.49, 95% CI, 0.45-0.54, C-index 0.68), as were International Federation of Gynaecology and Obstetrics (FIGO) stage and debulking surgery outcome. Three prognostic groups were identified based on the surgery outcome and KELIM score, with large differences in OS (105.1, ∼45.0, and 22.1 months) and PFS (58.1, ∼15.0, and 8.0 months). Surrogacy for OS and for PFS was not established.CONCLUSION: KELIM is an independent prognostic biomarker for survival, complementary to surgery outcome, representing a new determinant of first-line treatment success.
KW - CA-125
KW - KELIM
KW - Ovarian cancer
KW - Primary chemosensitivity
KW - Prognostic biomarker
KW - Surrogate end-point
UR - http://www.scopus.com/inward/record.url?scp=85168797549&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2023.112966
DO - 10.1016/j.ejca.2023.112966
M3 - Journal article
C2 - 37542936
SN - 0959-8049
VL - 191
SP - 1
EP - 11
JO - European journal of cancer (Oxford, England : 1990)
JF - European journal of cancer (Oxford, England : 1990)
M1 - 112966
ER -