Prognostic nomogram for progression-free survival in patients with BRCA mutations and platinum-sensitive recurrent ovarian cancer on maintenance olaparib therapy following response to chemotherapy
- Author(s)
- Tjokrowidjaja, A; Friedlander, M; Lord, SJ; Asher, R; Rodrigues, M; Ledermann, JA; Matulonis, UA; Oza, AM; Bruchim, I; Huzarski, T; Gourley, C; Harter, P; Vergote, I; Scott, CL; Meier, W; Shapira-Frommer, R; Milenkova, T; Pujade-Lauraine, E; Gebski, V; Lee, CK;
- Journal Title
- European Journal of Cancer
- Abstract
- BACKGROUND: The impact of maintenance therapy with PARP inhibitors (PARPi) on progression-free survival (PFS) in patients with BRCA mutations and platinum-sensitive recurrent ovarian cancer (PSROC) varies widely. Individual prognostic factors do not reliably distinguish patients who progress early from those who have durable benefit. We developed and validated a prognostic nomogram to predict PFS in these patients. METHODS: The nomogram was developed using data from a training patient cohort with BRCA mutations and high-grade serous PSROC on the placebo arm of two maintenance therapy trials, Study 19 and SOLO2/ENGOT-ov21. We performed multivariable Cox regression analysis based on pre-treatment characteristics to develop a nomogram that predicts PFS. We assessed the discrimination and validation of the nomogram in independent validation patient cohorts treated with maintenance olaparib. RESULTS: The nomogram includes four PFS predictors: CA-125 at randomisation, platinum-free interval, presence of measurable disease and number of prior lines of platinum therapy. In the training (placebo) cohort (internal validation C-index 0.64), median PFS in the model-predicted good, intermediate and poor-risk groups was: 7.7 (95% CI 5.3-11.3), 5.4 (4.8-5.8) and 2.9 (2.8-4.4) months, respectively. In the validation (olaparib) cohort (C-index 0.71), median PFS in the model-predicted good, intermediate and poor-risk groups was: not reached, 16.6 (13.1-22.4) and 8.3 (7.1-10.8) months, respectively. The nomogram showed good calibration in the validation cohort (calibration plot). CONCLUSIONS: This nomogram can be used to predict PFS and counsel patients with BRCA mutations and PSROC prior to maintenance olaparib and for stratification of patients in trials of maintenance therapies.
- Publisher
- Elsevier
- Keywords
- BRCA mutation; Nomogram; Olaparib; Ovarian cancer; Poly(ADP-ribose) polymerase inhibitors; Prognosis
- Research Division(s)
- Cancer Biology And Stem Cells
- PubMed ID
- 34293664
- Publisher's Version
- https://doi.org/10.1016/j.ejca.2021.06.024
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-08-16 10:40:58
Last Modified: 2021-08-16 11:29:48