Relationship of cancer stem cell functional assay and objective response rate of patients with recurrent platinum-resistant ovarian cancer in a randomized trial.
Authors: Herzog Thomas J. , Krivak Thomas C. , Diaz John Paul , Lentz Scott E , Bush Stephen , Nair Navya , Bou Zgheib Nadim , Gunderson Jackson Camille , Barve Abhijit J. , Lirette Seth T. , Howard Candace M. , Valluri Jagan , Denning Krista L , Claudio Pier Paolo 
Published: June 2024

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Background: Patients with recurrent platinum-resistant epithelial ovarian cancer (EOC) have poor clinical outcomes, owing in large part to the presence of therapy-resistant cancer stem cells (CSCs). A randomized clinical trial (NCT03949283) was conducted to determine if chemotherapy regimens guided by the CSCs functional assay (ChemoID) can improve objective response rate (ORR) in patients with recurrent platinum-resistant EOC when compared to empiric treatment selection. Methods: Patients with recurrent platinum-resistant EOC who had failed standard of care (SOC) therapy, were randomly assigned (1:1) to one of two intervention groups and given one of thirteen mono or combination chemotherapies based on the results of a ChemoID assay or physician choice. Fresh biopsy samples obtained from all subjects enrolled in the study were used to determine the sensitivity of CSCs and the bulk of tumor cells to the same panel of chemotherapies. Subjects randomized to the ChemoID-guided arm were treated with chemotherapies predicted by the assay while taking into consideration their health status, whereas treating physicians of subjects enrolled in the physician-choice arm were blinded to the test results. RECIST 1.1 response was assessed on CT scans. Results: The study met its primary endpoint at its first predetermined efficacy analysis by comparing the objective response rate (ORR) between treatment groups. The median ORR (mORR) of subjects treated with chemotherapies guided by the ChemoID assay was 55% (CI95 39% – 73%), compared to 5% (CI95 0% – 11%) for subjects treated with physician's choice chemotherapy with a p-value p<0.0001. The secondary endpoint analysis of duration of response (DOR) showed statistically significant differences (p<0.0001) between subjects treated with chemotherapies guided by the ChemoID assay versus subjects treated with physician’s choice chemotherapy with a median duration of response of 8 months vs. 5.5 months, respectively. The median clinical benefit rate (mCBR) of subjects treated with ChemoID-guided chemotherapies was 85% (CI95 73% – 97%) and the mCBR of subjects treated with chemotherapies empirically chosen by the physicians was 24% (CI95 11% – 38%) with a p-value <0.0001. No association was found between response and the number of prior platinum-based treatments (p = 0.651), age (p = 0.195), race (p = 0.173), or ECOG status (p = 0.938). The association between treatment groups and response was not modified by CA125 (p = 0.199) nor was CA125 itself associated with response (p = 0.187). Conclusions: These findings suggest that individually screening standard cytotoxic chemotherapy treatments with the ChemoID assay improves objective responses in recurrent platinum-resistant EOC patients. Clinical trial information: NCT03949283 .