Challenges in economic modeling of anticancer therapies: an example of modeling the survival benefit of olaparib maintenance therapy for patients with BRCA-mutated platinum-sensitive relapsed ovarian cancer.
OBJECTIVE
The aim of this paper is to describe a four health-state, semi-Markov model structure with health states defined by initiation of subsequent treatment, designed to make best possible use of the data available from a phase 2 clinical trial.


METHODS
The approach is illustrated using data from a sub-group of patients enrolled in a phase 2 clinical trial of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA mutation (NCT00753545). A semi-Markov model was developed with four health states: progression-free survival (PFS), first subsequent treatment (FST), second subsequent treatment (SST), and death. Transition probabilities were estimated by fitting survival curves to trial data for time from randomization to FST, time from FST to SST, and time from SST to death.


RESULTS
Survival projections generated by the model are broadly consistent with the outcomes observed in the clinical trial. However, limitations of the trial data (small sample size, immaturity of the PFS and overall survival [OS] end-points, and treatment switching) create uncertainty in estimates of survival.


CONCLUSIONS
The model framework offers a promising approach to evaluating cost-effectiveness of a maintenance therapy for patients with cancer, which may be generalizable to other chronic diseases.
HERON Commercialization, PAREXEL Consulting , London , UK.
Robert
R
Hettle
John
J
Posnett
John
J
Borrill
D000970:Antineoplastic Agents / Q000191:economics* / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D008390:Markov Chains; D017059:Models, Econometric; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D010793:Phthalazines / Q000191:economics* / Q000627:therapeutic use*; D010879:Piperazines / Q000191:economics* / Q000627:therapeutic use*; D016019:Survival Analysis
D000970:Antineoplastic Agents; D010793:Phthalazines; D010879:Piperazines; C531550:olaparib
Anti-cancer agents; Economic model; Olaparib; Ovarian cancer