A groundbreaking randomized clinical trial has demonstrated that ChemoID, a functional precision medicine assay that targets cancer stem cells, significantly improves outcomes for patients with recurrent platinum-resistant ovarian cancer, a condition associated with poor prognosis and limited treatment options.
The phase 3 trial (NCT03949283), published in npj Precision Oncology, enrolled 81 patients with recurrent platinum-resistant epithelial ovarian cancer who were randomized 1:1 to receive treatment guided either by the ChemoID assay or by physician's choice from the same panel of 13 chemotherapy regimens.
Remarkable Improvement in Response Rates
The results showed a dramatic improvement in the objective response rate (ORR) - the primary endpoint of the study. Patients in the ChemoID-guided group achieved an ORR of 50% (95% CI, 35%-65%) compared to just 5% (95% CI, 0%-11%) in the physician-choice group (p<0.0001).
"This is the first-in-human randomized trial to demonstrate that prospective interventional use of a functional precision medicine test such as the ChemoID assay to select effective treatments for poor prognosis patients with recurrent platinum-resistant ovarian cancer resulted in a significantly improved response rate," the researchers noted.
Significant Improvements Across Multiple Endpoints
Secondary endpoints also showed substantial benefits with ChemoID-guided therapy:
- Median progression-free survival (PFS) was 11.0 months in the ChemoID group versus 3.0 months in the physician-choice group (HR, 0.27; 95% CI, 0.15-0.49; p<0.001)
- Median duration of response (DOR) was 8 months with ChemoID versus 5.5 months with physician choice (p<0.0001)
- Clinical benefit rate (CBR), which includes complete responses, partial responses, and stable disease, was 83% with ChemoID versus 24% with physician choice (p<0.0001)
Targeting Cancer Stem Cells: A New Treatment Paradigm
The ChemoID assay represents a novel approach to cancer treatment by specifically targeting cancer stem cells (CSCs), which are implicated in chemotherapy resistance and disease recurrence. The assay tests the patient's live tumor cells, including both bulk tumor cells and CSCs isolated from tumor biopsies or malignant fluid aspirates, to determine which chemotherapy regimens would be most effective.
"The novelty of the ChemoID assay is its focus on CSCs, which are implicated in resistance to platinum-based therapies," the researchers explained. "The aggressiveness of recurrent epithelial ovarian cancer is mostly attributed to the presence of ovarian cancer stem cells, which are chemo-resistant and responsible for the recurrence of cancer."
Dr. Pier Paolo Claudio, a co-developer of the clinical test, explained: "The thought is that by testing the tumor for chemosensitivity in not only the tumor cells but also the cancer stem cells, one can eradicate the cancer stem cells that would repopulate the tumor."
Study Design and Patient Population
The trial enrolled adult females who had received at most five prior lines of therapy, including at least one platinum-based treatment. All patients enrolled had recurrent high-grade serous carcinoma, a common and aggressive form of ovarian cancer.
Fresh tissue samples were collected from each patient and divided into two portions - one for the ChemoID laboratory and one for histopathological confirmation. The ChemoID assay was performed on all enrolled subjects, with results available in a median of 14 days.
In the ChemoID-guided group, 50% of patients responded to treatment (18 partial responses and 2 complete responses), 32.5% had stable disease, and only 17.5% had progressive disease. In contrast, in the physician-choice group, 78% of patients had progressive disease, 19.5% had stable disease, and only 2.5% had a response to treatment.
Implications for Clinical Practice
The findings suggest that the ChemoID assay could provide more treatment options for patients with recurrent platinum-resistant ovarian cancer, a condition that typically has poor outcomes with standard approaches.
"This method of determining the responses of CSCs to available FDA-approved chemotherapies for the treatment of ovarian cancer provided critical information about an individual patient's likelihood of achieving a response that is more durable before implementing the patient's treatment plan," the researchers stated.
The researchers also noted that the approach could be particularly beneficial in the context of value-based healthcare models, as it focuses on optimizing the use of standard chemotherapies that are routinely covered by insurance and used by community oncologists globally, rather than requiring more expensive targeted therapies.
Future Directions
While the study demonstrates promising results, the researchers acknowledged some limitations, including the need for viable tumor samples and the current centralized laboratory processing. However, they noted that ongoing efforts aim to optimize the assay for broader implementation.
The researchers are also exploring an expanded panel of drugs to offer patients more flexibility and include newer agents in the future. They envision that personalized anti-cancer therapy targeting CSCs will be included earlier in treatment plans, eliminating ineffective treatments and allowing patients to gain the greatest therapeutic benefit possible.
This study represents a significant advance in the personalized treatment of recurrent platinum-resistant ovarian cancer, offering new hope for patients with this challenging condition.
