Frontline treatment with intraperitoneal chemotherapy is commonly underutilized for a majority of patients with optimally cytoreduced stage III ovarian cancer, despite recommendations for its use and a clear demonstration of improved overall survival.
Alexi Wright, MD, MPH
Utilization of frontline intraperitoneal (IP) chemotherapy has yet to gain widespread acceptance for a majority of patients with optimally cytoreduced stage III ovarian cancer, despite recommendations for its use and a clear demonstration of improved overall survival (OS), according to a prospective cohort study published in the Journal of Clinical Oncology.
Utilization of IP regimens began to increase in 2005 and spiked after 2006, based on more than a 16-month OS advantage seen with IP versus IV therapy in the GOG-172 trial. However, following this initial climb, IP/IV therapy usage plateaued at approximately 50%, according to the study.
“Unfortunately, fewer than half of women who qualify for IP/IV chemotherapy received the treatment. This suggests that increasing access to IP/IV chemotherapy may improve ovarian cancer patients’ survival,” said lead investigator Alexi Wright, MD, MPH, of the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute, in a statement.
OS trends were analyzed by treatment type using a propensity score—matched analysis to compensate for confounding factors. Of 823 patients originally assessed, 402 were eligible for the propensity analysis. In this group, the 3-year OS rates were 81% and 71% with IP/IV (n = 201) and IV chemotherapy (n = 201), respectively (HR, 0.68; 95% CI, 0.47-0.99; P = 0.47).
“This is the first study to show that IP/IV chemotherapy improves survival in the real world, outside of a clinical trial,” Wright said. “Use of the technique may be influenced by clinical practice leaders’ enthusiasm for intraperitoneal delivery. Our findings demonstrate the dual approach is an important and underutilized strategy for improving outcomes in ovarian cancer.”
Of the women who started IP/IV chemotherapy, 44% completed 6 or more cycles of therapy. Twenty-nine percent of patients received the same regimen that was administered in the GOG-172 trial (IV paclitaxel with IP cisplatin and paclitaxel). Other regimens contained substitutions, such as docetaxel instead of paclitaxel, lower doses of cisplatin, or carboplatin instead of cisplatin. The median number of IP/IV cycles was 5 and did not differ substantially from findings from the GOG-172 study (P = .83).
Although adverse events (AEs) were higher with IP/IV therapy versus IV therapy, differences were only statistically significant for catheter complications (0.5% vs 13.4%; P = .001) and anemia (5% versus 10.9%; P = .04). Twenty percent of patients discontinued IP/IV therapy due to toxicity versus 10% with IV treatment (adjusted odds ratio, 2.83; 95% CI, 1.47-5.47; P = .002). Additionally, those treated with IP/IV therapy were more likely to present with a distant recurrence compared with IV chemotherapy (58.8% vs 29.4%).
The AEs associated with IP/IV in the cohort study were significantly less frequent than in previous clinical trials, including the GOG-172, -114, and -104 trials. In these analyses, OS was improved with IP versus IV therapy; however, the rates of AEs were much higher, leading to treatment discontinuation.
"The problem with the last two intraperitoneal studies is that IP therapy was tremendously toxic, particularly in the last trial, where the frequency of grade 3/4 toxicity with IP therapy was substantially higher in almost every toxicity category," James Tate Thigpen, MD, professor of Medicine and director, Division of Oncology and Hematology, University of Mississippi School of Medicine, said during an OncLive Peer Exchange. "In fact, the clinical alert in 2006 that recommended IP therapy said they couldn't recommend any of the tested regimens."
In addition to the use of IP chemotherapy, another lingering question in the frontline treatment of patients with ovarian cancer is the role of bevacizumab (Avastin). To further flush out an optimal frontline strategy, the ongoing phase III GOG-252 study is assessing bevacizumab with either IV or IP chemotherapy for patients with advanced ovarian, fallopian tube, and primary peritoneal carcinoma (NCT00951496). Results from this investigation are expected within the next 6 months, Thigpen suggested.
"The whole purpose of the GOG-252 trial is to determine if you can modify the regimens and make them more tolerable and still retain the alleged advantage in terms of progression-free and overall survival," he said. "If everyone gets bevacizumab and bevacizumab eliminates the need for IP therapy, I think—and I can't speak for everyone—that the majority of people would opt to give the bevacizumab, Taxol, carboplatin, rather than go through all of the logistical challenges and toxicity of IP chemotherapy."
Wright AA, Cronin A, Milne DE, et al. Use and effectiveness of intraperitoneal chemotherapy for treatment of ovarian cancer [published online before print August 3, 2015]. J Clin Oncol. doi:10.1200/JCO.2015.61.4776.