OICR-supported Phase II trial uncovers how ovarian cancers become resistant to treatment, identifies new opportunities to personalize treatment for future patients

Clinician investigator Dr. Stephanie Lheureux has seen many women fight ovarian cancer – some who overcome the disease and unfortunately many who die. These women inspire Lheureux to find new effective treatments and to continue improving how we treat the disease.

One remarkable patient inspired the EVOLVE trial. After years of keeping her ovarian cancer in check, her cancer began to grow again, indicating that it had become resistant to the maintenance treatment she was on. Lheureux presented the option of palliative chemotherapy, as the latest guidelines suggest, but her patient declined – she wanted a different treatment that would allow her to have a healthy life outside of the hospital.

“This type of chemotherapy requires several visits to the hospital and it’s associated with side effects on patients’ hair, skin and nails,” says Lheureux, Clinician Investigator at the University Health Network’s Princess Margaret Cancer Centre. “This patient didn’t want to go on standard chemotherapy. She had participated in several clinical trials before, and she urged me to find her another option.”

Lheureux and collaborators set out to find an alternative. The first step was to understand how the patient’s tumour became resistant to the maintenance treatment, olaparib. In a small pilot study, published in the Journal of Clinical Oncology, they analyzed her tumour and ovarian tumours from two other patients, quickly realizing that these cancers can become resistant to treatment in different ways.

“We clearly saw that one approach wouldn’t fit all patients,” says Lheureux. “When we discuss these results with patients and we see patients’ cancers progressing on treatment, we are motivated to find out how these tumours become resistant so that we can find new ways to attack the disease.”

Based on their preliminary findings, the research group launched a new phase II trial, EVOLVE, one of the first to assess how ovarian tumours evolve resistance over time to olaparib and other drugs that are classified as PARP inhibitors.

With the support of OICR’s Ovarian Cancer Translational Research Initiative, they analyzed dozens of biopsies and found genomic indicators of resistance. Their results, which were recently published Clinical Cancer Research, indicate new opportunities for personalized ovarian cancer treatment.

“We found that ovarian cancers can evolve in unexpected ways,” says Lheureux. “We are now using this new knowledge to strategically target these mechanisms based on each patient’s unique needs.”

Lheureux and collaborators are now working to identify which patients will respond to different treatments through blood samples instead of tumour biopsies. A blood-based test could ultimately serve as a less-invasive alternative to biopsies, allowing clinicians and patients to predict when a tumour may become resistant to treatment and how best to outmaneuver the tumour’s next move.

“Our patients have been, and continue to be, the centre from which all our research endeavors arise from,” says Lheureux. “We are driven to understand and learn from each of our patients, and to honour their courage and commitment to making changes in the treatment of ovarian cancer for women living with disease and for those women who will be diagnosed.”