Evaluation of a chemoresponse assay as a predictive marker in the treatment of recurrent ovarian cancer: further analysis of a prospective study

Abstract

Background:Recently, a prospective study reported improved clinical outcomes for recurrent ovarian cancer patients treated with chemotherapies indicated to be sensitive by a chemoresponse assay, compared with those patients treated with non-sensitive therapies, thereby demonstrating the assay's prognostic properties. Due to cross-drug response over different treatments and possible association of in vitro chemosensitivity of a tumour with its inherent biology, further analysis is required to ascertain whether the assay performs as a predictive marker as well.Methods:Women with persistent or recurrent epithelial ovarian cancer (n=262) were empirically treated with one of 15 therapies, blinded to assay results. Each patient's tumour was assayed for responsiveness to the 15 therapies. The assay's ability to predict progression-free survival (PFS) was assessed by comparing the association when the assayed therapy matches the administered therapy (match) with the association when the assayed therapy is randomly selected, not necessarily matching the administered therapy (mismatch).Results:Patients treated with assay-sensitive therapies had improved PFS vs patients treated with non-sensitive therapies, with the assay result for match significantly associated with PFS (hazard ratio (HR)=0.67, 95% confidence interval (CI)=0.50–0.91, P=0.009). On the basis of 3000 simulations, the mean HR for mismatch was 0.81 (95% range=0.66–0.99), with 3.4% of HRs less than 0.67, indicating that HR for match is lower than for mismatch. While 47% of tumours were non-sensitive to all assayed therapies and 9% were sensitive to all, 44% displayed heterogeneity in assay results. Improved outcome was associated with the administration of an assay-sensitive therapy, regardless of homogeneous or heterogeneous assay responses across all of the assayed therapies.Conclusions:These analyses provide supportive evidence that this chemoresponse assay is a predictive marker, demonstrating its ability to discern specific therapies that are likely to be more effective among multiple alternatives.

Reduction of CA125 Levels During Neoadjuvant Chemotherapy Can Predict Cytoreduction to No Visible Residual Disease in Patients with Advanced Epithelial Ovarian Cancer, Primary Carcinoma of Fallopian tube and Peritoneal Carcinoma

“…Many studies have reported biomarkers that predict chemotherapeutic sensitivity, and some have even been clinically accepted. Unfortunately, none of the biomarkers have been clinically validated for use in EOC 25. In our study, we analyzed the relationship between five parameters of CA125 reduction and chemotherapeutic sensitivity and found that a preoperative CA125 of ≤200 U/ml was the only predictor of chemotherapy-sensitive disease in EOC patients with NAC-IDS, though, it was not the independent predictor.…”

In Vitro Chemosensitivity in Ovarian Carcinoma – Comparison of Three Leading Assays

“…In a study from USA with 262 patients, all the patients were treated empirically, but a chemosensitivity assay was also performed concomitantly for all. In addition, in the subgroup of patients treated with assay-sensitive agents, progression-free survival (PFS) and OS are found to be improved, and further analysis has confirmed these results (14,15). Recently, an observational study has also evaluated chemosensitivity profiles of type 1 and type 2 epithelial ovarian cancer (EOC) (16).…”

Evolution of Chemosensitivity and Resistance Assays as Predictors of Clinical Outcomes in Epithelial Ovarian Cancer Patients

“…Additional analyses of this trial evaluated the potential prognostic and predictive capabilities of the chemoresponse assay [64]. The association of the chemoresponse assay-predicted responses to the administered treatment (i.e., PFS) with actual patient outcomes (match condition) compared with a randomly selected chemoresponse assay result for the same patient (mismatch condition) was assessed.…”

“… CI, confidence interval; EOC, epithelial ovarian cancer; HR, hazard ratio; ICER/LYS, incremental cost-effectiveness rating per life-year saved; OS, overall survival; PFI, progression-free interval; PFS, progression-free survival. a Reference 64, b reference 61, c reference 63, d reference 58, e reference 11, f reference 62, g reference 66, h reference 65, i reference 25, j reference 68, k reference 67. …”