Improved Overall Survival With Primary Over Consolidation Intraperitoneal Chemotherapy After Optimal Cytoreduction for Advanced Ovarian Cancer


Key Points

  • Standard first-line therapy for patients with advanced epithelial ovarian cancer is primary cytoreductive surgery, although relapse occurs in about three-quarters of cases.
  • Primary intravenous (IV)/intraperitoneal (IP) chemotherapy was associated with longer overall survival than IV followed by consolidation IP chemotherapy in patients who underwent optimal primary cytoreductive surgery (78.8 vs 57.5 months).
  • There was no statistically significant difference in progression-free survival between treatment groups.

Compared with intravenous (IV) followed by consolidation intraperitoneal (IP) chemotherapy, primary IV/IP chemotherapy was associated with a statistically significant improvement in overall survival—but not progression-free survival—in patients with advanced epithelial ovarian cancer who underwent optimal primary cytoreduction, according to the results of a study in Gynecologic Oncology. Decreasing the time between primary debulking and the administration of IP chemotherapy may lead to better long-term outcomes, suggested Suidan et al, although randomized trials are needed to explore this issue further.

In the United States, most women diagnosed with primary epithelial ovarian, fallopian tube, or peritoneal carcinoma present with advanced-stage disease. Standard first-line therapy for these patients is primary cytoreductive surgery followed by a combination of platinum- and taxane-based chemotherapy. However, relapse occurs in about three-quarters of patients, with the majority of tumors confined to the peritoneal cavity.

Thus, the role of IP chemotherapy in the primary setting after cytoreductive surgery for advanced ovarian cancer has received much attention in clinical trials. As a result, the current management strategy at Memorial Sloan Kettering Cancer Center (MSKCC) in New York is to give IV/IP chemotherapy upfront after primary cytoreduction.

Study Details

To assess the long-term outcomes of patients with advanced epithelial ovarian cancer who underwent optimal debulking surgery, Suidan et al compared two treatment regimens: primary IV/IP chemotherapy vs IV followed by consolidation IP chemotherapy. Of the 224 patients treated at MSKCC, 72% (162 patients) received primary IV/IP chemotherapy, and 28% (62 patients) received IV followed by consolidation IP chemotherapy. In addition, the investigators reported no difference in residual disease between the two groups after cytoreductive surgery.

The primary IP regimen contained IV paclitaxel on day 1, IP cisplatin on day 2, and IP paclitaxel on day 8. The consolidation IP regimen included IV paclitaxel on day 1, IV carboplatin on day 1, and then second-look surgery; if no or small-volume (≤ 1 cm) residual disease was found, IP cisplatin was then given.

Taking a closer look at these patients, the median age was about 59 years in both groups. The investigators noted that serous tumors were significantly more common in the primary IV/IP chemotherapy group than in the consolidation IP group. In addition, the women in the consolidation IP group had a higher median preoperative platelet count, CA-125 level, and amount of ascites at presentation than those in the primary IP group.

Significant Benefit in Overall but Not Progression-Free Survival

At a median follow-up for the entire cohort of 50 months (range, 9–141 months), those in the primary IP group had a longer median progression-free survival than those in the consolidation IP group; however, it did not reach statistical significance (23.7 months vs 19.7 months; hazard ratio [HR] = 0.78; 95% confidence interval [CI] = 0.57–1.06; P = .11). As for the median overall survival, it was significantly longer for the primary IP group than the consolidation IP group (78.8 months vs 57.5 months; HR = 0.56; 95% CI = 0.38–0.83; P = .004).

Moreover, on univariate analysis, there was a significant association between progression-free survival and three other factors: histology, preoperative CA-125 value, and residual disease. There also was a significant relationship between overall survival and histology, preoperative platelet count, and residual disease.

The investigators reported that the difference in progression-free survival was not significant on multivariate analysis (HR = 0.78; 95% CI = 0.56–1.11; P = .17). On the other hand, the difference in overall survival remained significant on multivariate analysis (HR = 0.59; 95% CI = 0.39–0.89; P = .01).

Closing Thoughts

“Our data show an approximately 21-month overall survival benefit for the primary IP group and an approximately 4-month progression-free survival benefit for the same group,” stated the investigators. “It is possible that a larger patient cohort may have been needed to show a statistically significant progression-free survival difference, which was not needed to show an overall survival benefit, as the difference in survival between both groups was striking.”

The investigators proposed that by decreasing the time between primary debulking and the use of IP chemotherapy, survival outcomes may potentially improve. However, they acknowledged that future randomized trials should explore further the administration of IP chemotherapy at the time of such surgery or soon thereafter.

Rudy S. Suidan, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author of the article in Gynecologic Oncology.

This study was supported by the Roy M. Speer Foundation. The authors disclosed no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.