IP Chemo Improves Long-Term Outcomes in Ovarian Cancer

The added overall survival benefit seen with intraperitoneal versus intravenous chemotherapy extends beyond 10 years for patients with ovarian cancer.

Krishnansu S. Tewari, MD

The added overall survival (OS) benefit seen with intraperitoneal (IP) versus intravenous (IV) chemotherapy was still evident at a long-term analysis for patients with ovarian cancer, according to a median 10.7 year follow-up of a Gynecologic Oncology Group (GOG) study published in theJournal of Clinical Oncology.

The study retrospectively analyzed data from two phase III studies, GOG 114 and 172, which each contained patients treated with IP and IV chemotherapy. The analysis, conducted by Tewari et al, explored long-term OS, the extent of residual disease, and number of cycles of IP therapy. Overall, topline findings revealed that IP chemotherapy was associated with a 23% decreased risk of death compared with IV administered treatment.

Long-Term Outcomes Enumerated

"This report provides the first updated results of GOG IP chemotherapy trials, showing long-term survival benefit extending beyond 10 years," the authors of the study wrote. "Future results of the fourth phase III trial in GOG 252 will yield additional information regarding the incorporation of different approaches to IP therapy, including: dose-dense paclitaxel, antivascular targeted therapy, and maintenance therapy."The study examined 876 patients with advanced ovarian cancer with IP (n = 440) and IV (n = 436) chemotherapy. The median OS with IP therapy was 61.8 months compared with 51.4 months with IV treatment (adjusted HR = 0.77; 95% CI, 0.65-0.90;P= .002). The median progression-free survival was 25 and 20 months for the IP and IV arms (HR = 0.79; 95% CI, 0.67 to 0.92;P= .003)

In patients with gross residual disease (≤1 cm), IP chemotherapy improved OS by 25% versus IV treatment (adjusted HR = 0.75; 95% CI, 0.62 to 0.92;P= .006). However, patients with gross residual disease had a 1.89-fold increase in risk of death versus those with no visible disease (95% CI, 1.48 to 2.43;P< .001).

Factors Identified to Guide IP Treatment

"The long-term results of these trials are encouraging and provide additional support on the benefit of IP therapy while demonstrating that long-term survival end points are achievable in advanced ovarian cancer," the authors wrote.A number of factors were identified as being associated with worse outcomes, including clear/mucinous versus serous histology, gross residual versus no visible disease, and fewer versus more cycles of IP chemotherapy. Nearly half of patients did not complete IP therapy, due to side effects, the researchers noted.

In those who could tolerate the treatment, each additional cycle of IP therapy resulted in a 12% increase in overall outcomes. However, there was a 5% decrease in the probability of completing therapy with each year of age (odds ratio = 0.95; 95% CI, 0.93-0.96;P< .001), suggesting that younger patients were more likely to complete the IP regimen.

"Because our data showed that it is important to receive six cycles of IP therapy, we performed an analysis to identify factors associated with completing the IP regimen," the investigators wrote. "These findings may allow the clinician to better individualize IP therapy for those who will most likely complete and benefit from IP treatment and prevent unnecessary toxicity for those who will not tolerate this intensive regimen."

Tewari D, Java JJ, Salani R, et al. Long-Term Survival Advantage and Prognostic Factors Associated With Intraperitoneal Chemotherapy Treatment in Advanced Ovarian Cancer: A Gynecologic Oncology Group Study.J Clin Oncol. 2015;33(13):1460-1466.