LOS ANGELES – Patients with resected advanced ovarian cancer and low-volume residual disease fare better in the long term with intraperitoneal chemotherapy instead of intravenous chemotherapy.
A team led by Dr. Devansu Tewari assessed outcomes in 876 women from two key Gynecologic Oncology Group trials: GOG 114 and GOG 172. Combined median follow-up in those trials approached 11 years.
Compared with their peers given intravenous chemotherapy, women given intraperitoneal (IP) chemotherapy had a 16% lower risk of progression or death and a 17% lower risk of death, according to results reported at the annual meeting of the Society of Gynecologic Oncology.
Benefit was evident regardless of the extent of residual disease. Also, each additional cycle of IP chemotherapy reduced the risk of death by 12%.
Dr. Devansu Tewari
"A strength of this study is that it is a combined analysis of these two major IP trials that looked at long-term follow-up and showed survival outcomes that are quite significant. The defining difference between the two groups is that one received IP therapy and one did not, as it is very unlikely that IP therapy would have been administered in the recurrent setting," Dr. Tewari commented.
Although more than 7 years have elapsed since the National Cancer Institute recommended consideration of IP chemotherapy for advanced-stage low-volume ovarian cancer, uptake of this therapy has been limited given lingering questions about efficacy, safety, and issues such as the ideal regimen, noted Dr. Tewari, who is director of gynecologic oncology for the Southern California Permanente Medical Group in Orange County, California, and assistant professor of ob.gyn. at the University of California, Irvine.
"We have now updated the results of GOG 172 and GOG 114. But we also acknowledge that in the last 7 years, a lot has changed in the treatment of ovarian cancer in which these advantages may be further enhanced," he noted, for example, through use of bevacizumab (Avastin) and dose-dense therapy.
In particular, oncologists are awaiting results of the recently completed GOG 262 trial (assessing the role of bevacizumab and dose-dense paclitaxel) and the GOG 252 trial (assessing the role of IP carboplatin, bevacizumab, and dose-dense paclitaxel).
"We hope that the results of these studies, combined with the findings before, will bring in the foundation that we need to move forward in terms of laying the groundwork for treating women individually and tailoring their treatment for this cancer specifically for them," Dr. Tewari said.
One session attendee, noting the IP regimens used in the trials studied, asked, "Is it the dose-dense treatment or the IP that actually matters?"
"That’s a very good question. The whole issue with GOG 172 was essentially partial deployment of dose dense because patients [in the IP arm] received [an additional] day 8 treatment, so it has to be acknowledged," Dr. Tewari replied. "I think the answer is going to really come about when we see the findings of GOG 252."
Attendee Dr. Joan Walker of the University of Oklahoma, Oklahoma City, said, "I want to thank the presenters for emphasizing IP chemotherapy with cisplatin, and I think that it still needs to be emphasized."
She noted that the long-term survival gains being seen with IP chemotherapy are "just amazing. And we don’t know why that is, but obviously if GOG 104, 114, and 172 all show the same thing, it can’t necessarily be that the Taxol [paclitaxel] IP is the only contributing factor," she said.
"I think the future is bright for women and their survival, and it may be the bone marrow preservation of cisplatin that’s really causing the long-term effect because we know that patients get treated with multiple agents over and over again," Dr. Walker speculated.
The two trials that Dr. Tewari’s group studied – GOG 114 and GOG 172 – enrolled patients with resected stage III epithelial ovarian or peritoneal carcinoma who had residual disease measuring 1.0 cm or less.
The former trial compared IV carboplatin and paclitaxel with IP cisplatin; the latter trial compared IV paclitaxel with IP cisplatin and paclitaxel. About two-thirds of the women had macroscopic residual disease.
With a median follow-up of 10.7 years, relative to their counterparts given IV chemotherapy, women given IP chemotherapy had better progression-free survival (25 vs. 20 months; hazard ratio, 0.84; P = .03) and overall survival (62 vs. 51 months; hazard ratio, 0.83; P = .048).
The survival benefit of IP over IV chemotherapy was evident among both women with microscopic residual disease (5-year survival, 65% vs. 58%) and women with macroscopic residual disease (44% vs. 35%).