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Robert L. Coleman, MD, The University of Texas MD Anderson Cancer Center, discusses the next steps following results of the ARIEL2 trial, which aimed to identify patients with ovarian cancer most likely to respond to rucaparib using tumor genetic analysis.
Robert L. Coleman, MD, FACOG, FACS, professor, Ann Rife Cox Chair in Gynecology, Department of Gynecologic Oncology and Reproductive Medicine, vice chair, Clinical Research, The University of Texas MD Anderson Cancer Center, discusses the next steps following results of the ARIEL2 trial, which aimed to identify patients with ovarian cancer most likely to respond to rucaparib using tumor genetic analysis.
This research was used as a prospective decision tool that will also be implemented in the ongoing ARIEL3 trial, which will stratify patients based on their genomic score, BRCA mutation status, and loss of heterozygocity (LOH) score. The discovery of genomic “scarring” caused by homologous recombination deficiency as a biomarker in ARIEL2 will help move the next trial forward, Coleman explains. ARIEL2 will also be expanded to include more heavily pretreated patients.
To further improve the response rate, researchers are tweaking the trial design. Coleman says that even all BRCA-mutant patients did not respond to rucaparib. Also, in BRCA wild-type patients with a high degree of LOH, not all aberrant genes translated into response. These findings allow researchers to determine that not all genes involved in the pathway are representative of synthetic lethality.