Neoadjuvant chemotherapy was found equivalent to primary surgery followed by chemotherapy for patients with advanced ovarian cancer in the Medical Research Council Chemotherapy Or Upfront Surgery (MRC CHORUS) trial reported at the 2013 American Society of Clinical Oncology Annual Meeting. In this study, more patients who received neoadjuvant chemotherapy were able to undergo optimal debulking surgery and fewer had postoperative complications and deaths, but rates of progression-free survival (PFS) and overall survival (OS) were similar in both arms.
Lead author Sean Kehoe, MD, John Radcliffe Hospital, Oxford, United Kingdom, said that because these patients were, in general, older and sicker than in some other recent trials, neoadjuvant chemotherapy was a good option in this subpopulation. MRC CHORUS joins the EORTC 55971 trial as the second randomized trial to show noninferiority of neoadjuvant chemotherapy compared with primary surgery in advanced ovarian cancer, he noted.
From March 2004 to August 2010, 552 patients with stage III-IV ovarian cancer were enrolled in the MRC CHORUS trial. As 2 patients were randomized in error, the study population ultimately included 550 patients. Patients were randomized 1:1 to primary debulking surgery followed by 6 cycles of platinum-based chemotherapy (n=276) versus 3 cycles of neoadjuvant platinum-based chemotherapy followed by surgery and 3 cycles of chemotherapy (n=199).
Treatment arms had comparable baseline characteristics: median age was 65.5 years; 20% were WHO Performance Status 2-3; median tumor size was 8 cm; and 25% were stage IV. About 79% of those in the primary surgery arm and 68% of those in the neoadjuvant chemotherapy arm had high-grade serous carcinoma, which is particularly lethal.
In the primary surgery arm, 16% of patients underwent optimal debulking versus 40% in the neoadjuvant chemotherapy arm. Primary surgery was associated with more frequent toxicity, with 48% of patients experiencing grades 3 or higher toxicities versus 40% in the neoadjuvant chemotherapy arm. Grade 3 or 4 postoperative complications were reported in 24% of the primary surgery arm compared with 14% in the neoadjuvant chemotherapy arm.
Neoadjuvant chemotherapy also led to shorter hospital stays: discharge within 14 days was possible in 74% of those in the primary surgery arm versus 92% in the neoadjuvant chemotherapy arm. Also, deaths within 28 days of treatment numbered 5 (5.6%) in the primary surgery arm compared with 1 (0.5%) in the neoadjuvant chemotherapy arm.
The study also demonstrated noninferiority of neoadjuvant chemotherapy for survival outcomes: median PFS was 10.3 months for primary surgery versus 11.7 months for neoadjuvant chemotherapy, and OS was 22.8 months versus 24.5 months, respectively.
In formal discussions of this trial, Jonathan S. Berek, MD, director of the Stanford Women’s Cancer Center, California, said that the patients enrolled in the MRC CHORUS trial had a worse prognosis and were a bit older, suggesting that patient selection is important when considering neoadjuvant chemotherapy versus surgery as primary treatment for advanced ovarian cancer. l
Kehoe S, Hook J, Nankivell M, et al. Chemotherapy or upfront surgery for newly diagnosed advanced ovarian cancer: results from the MRC CHORUS trial. J Clin Oncol. 2013;31(suppl):Abstract 5500. Presented at: 2013 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2013; Chicago, IL.