GOG-252: Intravenous vs Intraperitoneal Chemotherapy in Advanced Ovarian Carcinoma
In the phase III NRG Oncology/Gynecologic Oncology Group (GOG)-252 study reported in the Journal of Clinical Oncology, Walker et al found no progression-free survival benefit of postsurgical intraperitoneal (IP) chemotherapy vs intravenous (IV) chemotherapy, each combined with bevacizumab, in patients with newly diagnosed advanced ovarian carcinoma.
Study Details
The open-label trial enrolled 1,560 women with epithelial ovarian, fallopian tube, and peritoneal carcinoma who had undergone surgery for staging and maximal cytoreduction. Patients were randomly assigned between July 2009 and November 2011 to receive six cycles of IV paclitaxel 80 mg/m2 once per week with IV carboplatin area under the curve = 6 (IV carboplatin group, n = 521), IV paclitaxel 80 mg/m2 once per week with IP carboplatin area under the curve = 6 (IP carboplatin group, n = 518), or once every 3 weeks IV paclitaxel 135 mg/m2 on day 1, IP cisplatin 75 mg/m2 on day 2, and IP paclitaxel 60 mg/m2 on day 8 (IP cisplatin group, n = 521). All patients received bevacizumab 15 mg/kg IV every 3 weeks in cycles 2 to 22.
The primary endpoint was progression-free survival, with an objective of determining whether IP chemotherapy improves progression-free survival in optimally resected (≤ 1 cm) advanced-stage disease.
Progression-Free Survival
Median follow-up was 84.8 months. Median progression-free survival was 24.9 months in the IV carboplatin group, 27.4 months in the IP carboplatin group (hazard ratio [HR] vs IV carboplatin = 0.925, 95% confidence interval [CI] = 0.802–1.07), and 26.2 months in the IP cisplatin arm (HR vs IV carboplatin = 0.977, 95% CI = 0.847–1.13). In the subgroup of 1,380 patients with stage II/III disease and residual disease of ≤ 1 cm or less, median progression-free survival was 26.9 months (IV carboplatin), 28.7 months (IP carboplatin), and 27.8 months (IP cisplatin). Median progression-free survival for patients with stage II/III with no gross residual disease was 35.9, 38.8, and 35.5 months, respectively.
Median overall survival was 75.5 months in the IV carboplatin group, 78.9 months in the IP carboplatin group (HR vs IV carboplatin = 0.949, 95% CI = 0.799–1.128), and 72.9 months in the IP cisplatin group (HR vs IV carboplatin = 1.05, 95% CI = 0.884–1.24), respectively. Overall survival was 80.0, 84.7, and 76.3 months, respectively, among patients with stage II/III and residual disease of ≤ 1 cm. Median survival was 98.8 months, 104.8 months, and not reached, respectively, among patients with stage II/III with no gross residual disease.
Adverse Events
Mean patient-reported Functional Assessment of Cancer Therapy (FACT)-Neurotoxicity scores were similar in all treatment groups. Mean Trial Outcome Index of the FACT-Ovary scores during chemotherapy were statistically worse in the IP cisplatin group. Grade ≥ 3 infections were more common in the IP cisplatin (17.7%) and IP carboplatin groups (17.2%) vs the IV carboplatin group (11.5%; overall P = .008). Grade ≥ 3 nausea and vomiting was more common (P < .005) in the IP cisplatin group vs the IV carboplatin and IP carboplatin groups (11.0% vs 5.1% and 4.7%). Grade ≥ 3 hypertension was more common (P < .005) in the IP cisplatin group vs the IV carboplatin and IP carboplatin groups (20.5% vs 11.9% and 14.3%).
The investigators concluded, “Compared with the IV carboplatin reference arm, the duration of [progression-free survival] was not significantly increased with either IP regimen when combined with bevacizumab and was better tolerated than IP cisplatin.”
Joan L. Walker, MD, of the Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit jco.ascopubs.org.
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®.
