A retrospective analysis showed that clinical participation was associated with improved overall survival compared to no trial participation among women with platinum-resistant epithelial ovarian cancer. These findings, which were recently presented during a scientific plenary session at the Society of Gynecologic Oncology's 54th Annual Meeting on Women's Cancer, highlight the need to prioritize clinical trials, particularly in this patient population.
"Ovarian cancer is the leading cause of gynecologic cancer mortality in the United States with a poor 5-year overall survival, often owed to advanced stage at the time of diagnosis and the eventual development of chemoresistance," noted study author Molly Morton, MD, a gynecology oncology fellow at The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute.
In patients with platinum-resistant ovarian cancer, she explained that the median survival is poor at 9-12 months, and currently approved therapies have limited efficacy with poor response rates of no more than 20-30 percent.
"Clinical trials allow us to treat patients with novel therapies and are an essential component of advancing oncologic care. Therefore, in ovarian cancer patients who have proven resistance to our most active therapies, they are best treated on clinical trials," Morton emphasized during her presentation. "While we know the importance of clinical trial participation, it is unknown whether participation in a clinical trial is associated with improvement in oncologic outcomes."
Study Methods
The objective of this IRB-approved, retrospective, single-institution cohort study was to determine if participation in any clinical trial is associated with the survival benefit in patients with platinum-resistant epithelial ovarian cancer.
This analysis included women who received treatment from January 1, 2009, to December 31, 2017, at the Cleveland Clinic. Platinum resistance was defined by the recurrence or progression of disease within 6 months of exposure to platinum-based chemotherapy, Morton explained. Clinical trial participation was defined as participation in any therapeutic clinical trial after the date of platinum resistance.
Study participants were divided into two cohorts: 1) clinical trial participants for platinum-resistant epithelial ovarian cancer, or 2) no clinical trial participation. Patients were included once in the clinical trial cohort regardless of the number of trials they had enrolled in. Individuals who did not participate in a clinical trial were considered the standard-of-care cohort.
"Demographic and oncologic variables were collected and overall survival was defined from the time of platinum resistance to death or last follow-up," Morton said. "Univariate and multivariate analyses were performed."
Key Findings
Of 305 eligible women with recurrent platinum-resistant epithelial ovarian cancer, 46 (15.1%) were clinical trial participants and 259 patients did not participate in clinical trials and were considered the standard-of-care cohort, according to Morton. The study authors observed no significant differences in baseline demographic characteristics, such as age, body mass index, race, functional status, or comorbid conditions between the two groups. Additionally, there were no significant differences in the original stage, histology, or the presence of germline mutations.
The rates of primary cytoreduction and residual disease at primary surgery, as well as the use of HIPEC and intraperitoneal chemotherapy, did not differ significantly between trial participants and the standard-of-care cohorts.
In terms of treatment demographics, the study investigators noted no significant differences between the use of PARP inhibitors or bevacizumab among either patient group. Patients in both groups underwent similar rates of secondary cytoreductive surgery, according to Morton.
"There were no differences between groups in regard to the time to platinum resistance from primary cytoreductive surgery, with a median of 28.5 months for trial participants and 25 months for those from the standard-of-care cohort," Morton explained. "Clinical trial participants were exposed to a greater number of total lines of therapy and median time on trial was 3.9 months."
Researchers calculated overall survival from the time of platinum resistance to death or last follow-up, with a median follow-up of 40 months. Morton and colleagues found that clinical trial participation was associated with significantly improved overall survival (13.8 months) compared with standard of care (10.5 months).
Morton acknowledged the limitations of their research, including the small sample size and single institution patient cohort, as well as the retrospective nature of the study. Other potential limitations include clinical trial enrollment bias and homogenous cohorts.
"In the future, we hope to expand our analyses to include a multi-institution patient cohort to confirm our results and evaluate these findings in other disease sites," Morton said. "Additionally, the association of clinical trial participation and improved survival in our cohort further underscores the importance of expanded access to clinical trials.
"Better understanding of the benefits of clinical trials may lead to improved counseling and, ultimately, earlier and improved enrollment in clinical trials," she added, while emphasizing the importance of recognizing the role of the provider in clinical trial enrollment. "It starts with us. Data suggests that about 50 percent of patients with gynecologic cancer report never having had a discussion with their provider about clinical trial participation."
Concluding her presentation, Morton said, "Clinical trial participation was associated with improved survival in patients with platinum-resistant epithelial ovarian cancer in a retrospective, single-institution cohort. Our data suggest that clinical trial participation should be prioritized in the platinum-resistant patient population when possible."
Catlin Nalley is a contributing writer.