Among 25 patients given an experimental combination of drugs for serous ovarian cancer, almost half experienced a significant reduction in tumor size. Although the trial was small, the results are exciting because all patients had tried other treatments without success.
Chemotherapy and hormone treatments for ovarian cancer have low success rates compared to other cancers, and ovarian cancer claims an estimated 160,000 lives each year.
In phase I of the FRAME trial, participants were given a combination of the drugs VS-6766 and defactinib. Results of the study were presented at the European Society for Medical Oncology Progress held over the weekend. Significant tumor shrinkage was observed in nearly half the patients – although, with such a small size, estimates of effectiveness frequency are rough. On average, patients went 23 months without tumors getting worse.
We may learn more soon, however. Recruitment has begun for a phase II trial, which will involve 100 participants to gain a better idea of how common the benefits are, starting this December and planning to finish in 2025. The trial will compare the combination of the two drugs with VS-6766 alone.
“If these findings are confirmed in larger trials, they’ll represent a significant advance in low-grade serous ovarian cancer treatment,” said Team Leader in Women’s Cancers at The Institute of Cancer Research Dr Susana Banerjee in a statement. “We’re very hopeful that this could become the standard of care for women with low-grade serous ovarian cancer.”
Phase I trials are primarily about testing for treatment safety, rather than effectiveness, so to observe such substantial benefits was a pleasant surprise.
Low grade serous ovarian cancer is not the most common form of ovarian cancer, but it tends to strike at an earlier age than other cancers of the ovaries, and is particularly hard to treat. Only around one in eight low grade serous ovarian cancer patients respond to chemotherapy, and one in seven to hormone therapy, leaving doctors with little beyond surgery for the majority of patients.
Drugs are most useful if doctors know beforehand which patients are most likely to respond, and the results raise the possibility this could be the case here. Some of those in the trial had the KRAS mutation, which is associated with a quarter of all tumors. Sixty-four percent of trial participants with the KRAS mutation experienced tumor shrinkage, but since this is from a sample of just 11, the number needs to be treated with considerable caution.
MEK inhibitors that block cancer's signaling pathway cause initial shrinkage in many cancers, but lose effectiveness as tumors develop resistance. It is thought defactinib may prevent resistance developing, allowing VS-6766 to stop the tumor's growth, opening the door to fighting may other hard-to-treat forms of cancer.