IP Chemo Improves Long-Term Survival in Ovarian Cancer

Devansu Tewari, MD

Women with advanced ovarian cancer lived almost a year longer when treated with intraperitoneal (IP) chemotherapy instead of intravenous (IV) therapy, long-term follow-up from two randomized trials showed. The data were presented at the 2013 Annual Meeting of the Society of Gynecologic Oncology (SGO).

IP chemotherapy led to a median overall survival of 62 months compared with 51 months for IV therapy. IP treatment also slowed disease progression by 25% versus IV treatment, study author Devansu Tewari, MD, reported at the SGO meeting.

“Each of these trials demonstrated a significant advantage for intraperitoneal chemotherapy,” said Tewari, assistant professor of Obstetrics and Gynecology at the University of California, Irvine. “In this combined analysis, the survival advantage extends to a median follow-up past 10 years.”

The data also confirmed the importance of completing IP therapy, as the survival advantage increased with the number of cycles of therapy.

The results came from a combined analysis of the Gynecologic Oncology Group (GOG) 114 and 172 trials. GOG 114 compared IV cisplatin-paclitaxel versus a combination of IV carboplatin, IV paclitaxel, and IP cisplatin (J Clin Oncol. 2001;19:1001-1007). GOG 172 compared IV cisplatin-paclitaxel and a regimen consisting of IV paclitaxel followed by IP cisplatin-paclitaxel.

Both trials had progression-free survival (PFS) as their primary endpoint, and survival was a secondary endpoint. The trials involved a combined total of 876 women with stage III epithelial ovarian carcinoma, optimally resected to ≤1 cm residual tumor.

Tewari reported findings from a median follow-up of 13.8 years in GOG 114 and 9.7 years in GOG 172. The primary results of the individual trials showed a 5.5- to 6-month improvement in median PFS with IP therapy. In the combined analysis, the data continued to show a 5-month difference in favor of IP therapy (25 vs 20 months). After adjustment, the difference translated into a 16% reduction in the hazard ratio for progression (P = .03).

The initial reports of survival data showed an 11-month difference in favor of IP therapy in GOG 114 and a 16-month advantage for IP in GOG 172. In an adjusted analysis of the long-term follow-up data from both trials, patients receiving IP chemotherapy had a 17% lower mortality risk (P = .048).

Tolerance has been problematic with IP chemotherapy from the first clinical evaluations, an issue reflected in the data from GOG 114 and 172. The 5-year survival rate among patients treated with IP therapy increased from 18% with completion of one or two cycles to 33% with three or four cycles, to 59% for patients who completed five or six cycles of treatment. In GOG 172, only 42% of patients in the IP arm completed the planned six cycles of therapy.

Several ongoing studies are focusing on optimizing IP chemotherapy by evaluating different doses and different drug combinations.

In a discussion following Tewari’s presentation, Joan Walker, MD, noted that the consistency of the results from GOG 114, GOG 172, and the earlier GOG 104 trial have been encouraging, but “it can’t necessarily be [that] the IP therapy is the only contributing factor [to the survival improvement].”

“I don’t think this is going to be the end of the story,” said Walker, professor of Medicine at the University of Oklahoma in Oklahoma City.

Tewari D, Java J, Salani R, et al. Long-term survival advantage of intraperitoneal chemotherapy treatment in advanced ovarian cancer: an analysis of a Gynecologic Oncology Group ancillary data study (GOG#114/172, abstract). Presented at: 2013 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 9-12, 2013; Los Angeles, CA. Abstract 6.