Results of a Phase II Trial Testing the Resensitization With Trabectedin in Platinum-resistant Ovarian Cancer

by Selleckchem | Jun 26 2023

Background/aim: In patients with advanced platinum-resistant ovarian cancer we prospectively evaluated whether trabectedin could resensitize the tumor cells to platinum rechallenge.

Patients and methods: Upon progression to platinum-based chemotherapy, trabectedin was administered as a 3-hour infusion every three weeks and subsequently crossed over to carboplatin/carboplatin-based combinations. The primary endpoints comprised objective response rate (ORR) and time to progression after trabectedin (TTP Trab). Secondary endpoints included ORR following platinum post-trabectedin, the growth modulation index (GMI) assessed as the ratio of successive TTP to platinum, given after (TTP2) and before (TTP1) trabectedin, quality of life (QoL), and ancillary translational studies.

Results: Ten patients with platinum-resistant ovarian cancer from a single institution were treated with trabectedin, one of whom achieved a partial response (PR) reaching the ORR of 10% and six had stable disease (SD) for a disease control rate (DCR) of 70%. After the treatment with platinum post-trabectedin, one patient achieved a PR and two had SD, attaining a rate of resensitization to platinum of 37.5%. The median TTP with trabectedin treatment was 15.0 weeks, while eight patients who received platinum post-trabectedin had the median TTP2 of 19.9 weeks. One patient reached the threshold of GMI >1 (12.5%) as indicator of clinical benefit. QoL of patients was not deteriorated with trabectedin. Predictive biomarkers of response to trabectedin and/or re-exposure to platinum could not be identified.

Conclusion: Although trabectedin did not achieve a wide resensitization to platinum in this heavily pretreated platinum-resistant population, a significant number of patients attained disease control.

Comments:

The study aimed to assess whether the drug trabectedin could resensitize tumor cells to platinum-based chemotherapy in patients with advanced platinum-resistant ovarian cancer. The primary endpoints of the study were the objective response rate (ORR) and time to progression after trabectedin (TTP Trab). Secondary endpoints included ORR following platinum-based chemotherapy post-trabectedin, the growth modulation index (GMI), quality of life (QoL), and ancillary translational studies.

Ten patients with platinum-resistant ovarian cancer were enrolled in the study and treated with trabectedin. Among these patients, one achieved a partial response (PR), resulting in an ORR of 10%, and six had stable disease (SD), leading to a disease control rate (DCR) of 70%. Following treatment with platinum-based chemotherapy post-trabectedin, one patient achieved a PR, and two had SD, indicating a resensitization rate to platinum of 37.5%. The median TTP with trabectedin treatment was 15.0 weeks, while the median TTP after receiving platinum-based chemotherapy post-trabectedin was 19.9 weeks among eight patients. One patient achieved a growth modulation index (GMI) greater than 1 (12.5%), which is considered an indicator of clinical benefit. The quality of life of patients did not deteriorate with trabectedin treatment. The study was unable to identify predictive biomarkers of response to trabectedin or re-exposure to platinum.

In conclusion, while trabectedin did not lead to a significant resensitization to platinum-based chemotherapy in this heavily pretreated platinum-resistant ovarian cancer population, a substantial number of patients achieved disease control with the treatment.