The use of a chemoresponse assay to assess therapy choices for patients with recurrent ovarian cancer correlated with dramatic improvements in overall survival (OS) and progression-free survival (PFS), according to a prospective clinical study. Researchers said the study showed that diagnostic testing could help clinicians individualize therapy in a tumor type where there are many equivalent treatment choices.
The study was designed to evaluate the effectiveness of the ChemoFx assay, a drug response marker in which patients’ tumor samples are tested for sensitivity and resistance to various chemotherapeutic agents. Results were reported in a manuscript accepted by the journal Gynecologic Oncology
, with an early version published online.
To evaluate the assay, researchers at Yale School of Medicine in Connecticut and more than 30 other cancer centers throughout the United States enrolled 262 evaluable patients between 2004 and 2011.
Eligible participants were diagnosed with epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that was persistent, recurrent, or progressive, and had received ≤2 prior chemotherapy regimens. The study included patients with platinum-sensitive disease, defined as a platinum-free interval (PFI) ≥6 months, and with platinum-resistant disease, defined as PFI <6 months.
Patients received one of 15 protocol-designated treatments that were empirically selected by their oncologists, who in turn were blinded to the assay results. The assay classified the treatments as either sensitive (S), intermediate (I), or resistant (R). Patient outcomes with the physician-selected treatments were then correlated with the assay results.
The study found that patients who were treated with an S regimen had significantly improved OS and PFS, whereas there was no difference in clinical outcomes for patients treated with regimens classified as I or R.
The median OS was 37.5 months for S compared with 23.9 months for I + R, a statistically significant improvement of 13.6 months (hazard ratio [HR] = 0.61; 95% CI, 0.41-0.89; P
= .010). The median PFS was 8.8 months for S compared with 5.9 months for I + R (HR = 0.67; 95% CI, 0.50-0.91; P
Additionally, the study found that the association with in vitro response was consistent among both platinum-sensitive patients (HR = 0.71) and platinum-resistant patients (HR = 0.66; P
= .690 for interaction test).
“This clinical study is a landmark for the treatment of ovarian cancer because it is the first prospective data that definitively show that a personalized diagnostic test can make a significant clinical impact by improving overall survival by 65% in women with this devastating cancer,” said lead investigator Thomas J. Rutherford, MD, PhD, professor of Obstetrics, Gynecology, and Reproductive Sciences, and section chief of Gynecologic Oncology at Yale, in a statement.
Need for Assays Stressed
Thus far, the clinical utility of chemoresponse assays in recurrent epithelial ovarian cancer has been controversial, with inconsistent findings on the correlation between test results and patient outcomes in several retrospective studies, Rutherford et al observed.
Nevertheless, the need for new diagnostic tools is pressing, the researchers indicated. It is the leading cause of gynecologic cancer mortality in the United States, with a majority of patients experiencing recurrences despite many available treatment strategies, investigators noted.
Moreover, current regimens for treating recurrent disease are based primarily on such factors as the patient’s treatment-free interval, anticipated toxicities, and clinical trial data, the researchers said. “As many as 20 different clinically acceptable and equivalent treatment choices are identified in current treatment guidelines, with insufficient evidence to indicate that any agent is superior to any other,” investigators said in the paper.
The authors noted that approximately 25% to 30% of participants were clinically responsive to their empirically selected chemotherapy, which is consistent with previous clinical studies that have looked at a mixture of platinum-sensitive and platinum-resistant patients. However, in this study, an additional 25% of patients tested S to at least one of the 15 chemotherapies but were treated with an I or R therapy empirically, suggesting that assay-informed individualized chemotherapy may provide a substantial benefit to patients and could be available for patients who are not receiving this therapy currently.
“If the oncologists had not been blinded to the results of the chemoresponse assay in this study, the number of patients who could have benefited from an S treatment would have more than doubled,” the researchers said.
ChemoFx is manufactured by Precision Therapeutics, Inc, based in Pittsburgh, Pennsylvania. The study authors include two company employees as well as approximately 10 coauthors who received compensation from Precision Therapeutics for participating in the clinical trial, according a conflict of interest statement in the article.
Rutherford T, Orr J, Grendys E, et al. A prospective study evaluating the clinical relevance of a chemoresponse assay for treatment of patients with persistent or recurrent ovarian cancer [published online ahead of print August 13, 2013]. Gyn Oncol. doi:10.1016/j.ygyno.2013.08.009.