Assay-Sensitive Treatment Improves Outcomes in Recurrent Ovarian Cancer
The use of assay-sensitive treatment significantly improved both progression-free survival and overall survival compared with nonsensitive treatment in women with recurrent ovarian cancer, according to the results of a prospective clinical trial reported in Gynecologic Oncology. Thomas Rutherford, MD, PhD, of Yale University School of Medicine, and colleagues suggest that diagnostic testing with chemoresponse assays may be a useful tool for optimizing the selection of treatment for both platinum-sensitive and platinum-resistant patients with persistent or recurrent ovarian cancer.
Study Findings
A total of 335 patients with histologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer from 35 sites across the United States took part in this clinical trial. Eligible patients received at least two prior chemotherapy regimens and experienced persistent, recurrent, or progressive disease, which was documented via imaging or an increased level of cancer antigen 125 (CA-125). Patients with both platinum-sensitive and platinum-resistant diseases, based on clinical outcomes after treatment in the primary setting, were included.
Based on the medical judgment of the oncologist, patients were treated with 1 of 12 distinct chemotherapies, which included both single agents and two-agent combinations. Thus, patients and physicians were blinded to the assay results for the initial protocol treatment. Fifty-five percent of patients had platinum-sensitive recurrent epithelial ovarian tumors.
The most commonly used regimens for platinum-sensitive tumors were carboplatin/paclitaxel, pegylated liposomal doxorubicin, and carboplatin/gemcitabine. The most frequently used regimens for persistent or platinum-resistant recurrent tumors were carboplatin/paclitaxel, pegylated liposomal doxorubicin, and topotecan. The investigators noted that no single treatment accounted for more than 30% of the treatments assessed in this study, suggesting a lack of a standard of care in this patient population.
At the time of tumor recurrence, fresh tissue samples were collected from each patient for in vitro testing. Of all eligible patients, 78% (262) had a successful assay and were evaluated for this study. The other 22% were excluded, primarily as a result of lack of growth of a sufficient number of malignant cells in culture and quality control failure. Most tumors were high-grade papillary serous.
After a median follow-up of 29 months, the median progression-free survival for the total study population was 6.7 months, and the median overall survival was 26.5 months. For platinum-sensitive and platinum-resistant patients, the median progression-free survival rates were 9.3 months and 3.8 months (P < .001), respectively, and the median overall survival rates were 33.6 months and 21.8 months (P < .001), respectively.
The assay result for the clinical treatment received was sensitive (28.6%), intermediate (45.8%), or resistant (25.6%). Based on univariate analysis, patients with tumor response defined as sensitive for their clinical treatment had a significant improvement in progression-free survival of about 3 months compared with those whose tumor response was defined as intermediate or resistant (8.8 vs 5.9 months; hazard ratio [HR] = 0.67; 95% confidence interval [CI] = 0.50–0.91; P = .009). An improvement in overall survival of about 14 months was also reported (37.5 months for sensitive vs 23.9 months for intermediate or resistant; HR = 0.61; 95% CI = 0.41–0.89; P = .010).
Clinical Implications
The use of in vitro chemoresponse assays for informing effective treatment selection for patients with recurrent ovarian cancer is a topic of debate among oncologists, stated Dr. Rutherford and colleagues. In their study, more than 50% of the tumors were found to be sensitive to at least one drug tested in vitro, suggesting that many patients with recurrent ovarian cancer may benefit from assay-informed individualized chemotherapy.
The investigators concluded, “A chemoresponse assay may be a very useful tool for optimizing treatment selection when there are multiple clinically acceptable and equivalent treatments available and few, if any, biological markers that can reliably assist in a more individualized treatment plan.”
ChemoFx is manufactured by Precision Therapeutics, Inc., which sponsored this clinical trial. According to the conflict of interest statement in this article, many of the study authors disclosed ties to Precision Therapeutics, Inc.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
