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. 2019 May 28:13:1179554919852071.
doi: 10.1177/1179554919852071. eCollection 2019.

Tumor Size and Overall Survival in Patients With Platinum-Resistant Ovarian Cancer Treated With Chemotherapy and Bevacizumab

Alexandre Sostelly  1 , François Mercier  1
Affiliations

Tumor Size and Overall Survival in Patients With Platinum-Resistant Ovarian Cancer Treated With Chemotherapy and Bevacizumab

Alexandre Sostelly et al. Clin Med Insights Oncol. .

Abstract

Introduction: Ovarian cancer is now recognized as a constellation of distinct subtypes of neoplasia involving the ovary and related structures. As a consequence of this heterogeneity, the analysis of covariates influencing the overall survival is crucial in this disease segment. In this work, an overall survival model incorporating tumor kinetics metrics in patients with platinum-resistant ovarian cancer was developed from the randomized, open label, phase 3 AURELIA trial.

Methods: Tumor size data from 361 patients randomly allocated to the bevacizumab + chemotherapy or chemotherapy study arm were collected at baseline and every 8 to 9 weeks until disease progression. Patients continued to be followed for survival after treatment discontinuation. A landmarked Cox proportional hazard survival model was developed to characterize the overall survival distribution.

Results: Two sets of factors were found to be influential on survival time: those describing the type and severity of disease (Eastern Cooperative Oncology Group [ECOG], Féderation Internationale de Gynécologie et d'Obstétrique [FIGO] stages, presence of ascites) and those summarizing the key features of the tumor kinetic model (tumor shrinkage at week 8 and tumor size at treatment onset). The treatment group was not required in the final model as the drug effect was accounted for in the tumor kinetics model.

Conclusions: This work has identified both ascites and tumor kinetics metrics as being the 2 most influential factors to explain variability in overall survival in patients with platinum-resistant ovarian cancer.

Keywords: angiogenesis; anti-angiogenesis; ovarian cancer; overall survival; therapy; tumor kinetics.

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Conflict of interest statement

Declaration Of Conflicting Interests:The author(s) declared following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Alexandre Sostelly and François Mercier were employed by F. Hofmann-La Roche Ltd.

Figures

Figure 1.
Figure 1.
Concordance index (overall c-index) obtained with different OS models.
Figure 2.
Figure 2.
Predicted probability of survival for various levels of ETS8 (%) in absence of ascites. Shaded areas correspond to the parametric 95% confidence interval around the mean probability.
Figure A1.
Figure A1.
Goodness-of-fit of the final model to the SLD values for a random sample of 9 patients from the AURELIA study. The curve depicts the model predicted SLD over time. The dots are the observations. SLD indicates sum of longest diameters.
Figure A2.
Figure A2.
Goodness-of-fit of the final model to the SD values: observations vs individual model predicted SLD. SLD indicates sum of longest diameters.
Figure A3.
Figure A3.
Goodness-of-fit of the final model to the SD values: Q-Q plot of CWRES.
Figure A4.
Figure A4.
Goodness-of-fit of the final model to the SD values: CWRES.
Figure A5.
Figure A5.
Distributions of observed vs predicted SLD values obtained from the “baseline” scan and from the first scan on treatment (at week 8).
Figure A6.
Figure A6.
Histogram of ETS8.
See this image and copyright information in PMC

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