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

Tian C, Sargent DJ, Krivak TC, Powell MA, Gabrin MJ, Brower SL, Coleman RL - Br. J. Cancer (2014)

Bottom Line: Women with persistent or recurrent epithelial ovarian cancer (n=262) were empirically treated with one of 15 therapies, blinded to assay results.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.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.

View Article: PubMed Central - PubMed

Affiliation: Precision Therapeutics, Inc., 2516 Jane Street, Pittsburgh, PA 15203, USA.

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.

Show MeSH

Related in: MedlinePlus

PFS for patients displaying homogeneous vs heterogeneous assay responses. Patients were classified into four groups based on their calculated multiple drug response index (MDRI) and administered clinical treatment: sensitive to all assayed therapies (MDRI=100%) and treated with a sensitive therapy (SA), sensitive to some therapies (0<MDRI<100%) and treated with a sensitive therapy (SP), non-sensitive to all therapies (MDRI=0) and treated with a non-sensitive therapy (RA), and non-sensitive to some therapies (0<MDRI<100%) and treated with a non-sensitive therapy (RP).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4150278&req=5

fig3: PFS for patients displaying homogeneous vs heterogeneous assay responses. Patients were classified into four groups based on their calculated multiple drug response index (MDRI) and administered clinical treatment: sensitive to all assayed therapies (MDRI=100%) and treated with a sensitive therapy (SA), sensitive to some therapies (0<MDRI<100%) and treated with a sensitive therapy (SP), non-sensitive to all therapies (MDRI=0) and treated with a non-sensitive therapy (RA), and non-sensitive to some therapies (0<MDRI<100%) and treated with a non-sensitive therapy (RP).

Mentions: Assay tumour responses differ by therapy, and cross-drug resistance was evident in this population. Of 262 tumours, 123 (47%) were identified as non-sensitive to all tested therapies (RA), whereas 24 (9%) were defined as sensitive to all tested therapies (SA); the remainder (44%) were sensitive to at least one therapy. For those patients showing a heterogeneous pattern of response, 51 were treated with sensitive therapies (SP), and 64 were treated with non-sensitive therapies (RP). The median PFS was 9.1, 8.8, 5.9 and 5.9 months for SA, SP, RP and RA, respectively, with significant difference between SA+SP vs RA+RP, as previously shown (HR=0.67, 95% CI=0.50–0.91, P=0.009; Rutherford et al, 2013), as well as approximately 3 months difference between SA vs RA and between SP vs RP, but without meaningful differences between SP vs SA or between RP vs RA (Figure 3).


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

Tian C, Sargent DJ, Krivak TC, Powell MA, Gabrin MJ, Brower SL, Coleman RL - Br. J. Cancer (2014)

PFS for patients displaying homogeneous vs heterogeneous assay responses. Patients were classified into four groups based on their calculated multiple drug response index (MDRI) and administered clinical treatment: sensitive to all assayed therapies (MDRI=100%) and treated with a sensitive therapy (SA), sensitive to some therapies (0<MDRI<100%) and treated with a sensitive therapy (SP), non-sensitive to all therapies (MDRI=0) and treated with a non-sensitive therapy (RA), and non-sensitive to some therapies (0<MDRI<100%) and treated with a non-sensitive therapy (RP).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150278&req=5

fig3: PFS for patients displaying homogeneous vs heterogeneous assay responses. Patients were classified into four groups based on their calculated multiple drug response index (MDRI) and administered clinical treatment: sensitive to all assayed therapies (MDRI=100%) and treated with a sensitive therapy (SA), sensitive to some therapies (0<MDRI<100%) and treated with a sensitive therapy (SP), non-sensitive to all therapies (MDRI=0) and treated with a non-sensitive therapy (RA), and non-sensitive to some therapies (0<MDRI<100%) and treated with a non-sensitive therapy (RP).
Mentions: Assay tumour responses differ by therapy, and cross-drug resistance was evident in this population. Of 262 tumours, 123 (47%) were identified as non-sensitive to all tested therapies (RA), whereas 24 (9%) were defined as sensitive to all tested therapies (SA); the remainder (44%) were sensitive to at least one therapy. For those patients showing a heterogeneous pattern of response, 51 were treated with sensitive therapies (SP), and 64 were treated with non-sensitive therapies (RP). The median PFS was 9.1, 8.8, 5.9 and 5.9 months for SA, SP, RP and RA, respectively, with significant difference between SA+SP vs RA+RP, as previously shown (HR=0.67, 95% CI=0.50–0.91, P=0.009; Rutherford et al, 2013), as well as approximately 3 months difference between SA vs RA and between SP vs RP, but without meaningful differences between SP vs SA or between RP vs RA (Figure 3).

Bottom Line: Women with persistent or recurrent epithelial ovarian cancer (n=262) were empirically treated with one of 15 therapies, blinded to assay results.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.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.

View Article: PubMed Central - PubMed

Affiliation: Precision Therapeutics, Inc., 2516 Jane Street, Pittsburgh, PA 15203, USA.

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.

Show MeSH
Related in: MedlinePlus