This is the second randomized controlled noninferiority trial to indicate that neoadjuvant chemotherapy is an alternative to primary surgery.
—Sean Kehoe, MD
Patients with newly diagnosed advanced ovarian cancer—especially patients with poor performance status—appear to derive benefits from neoadjuvant chemotherapy followed by surgery vs primary surgery followed by chemotherapy, according to results of the Medical Research Council (MRC) CHORUS trial. In the study, neoadjuvant chemotherapy improved operative debulking rates and operative morbidity and mortality compared with primary surgery, but median survival remained low in all patients.
“This is the second randomized controlled noninferiority trial to indicate that neoadjuvant chemotherapy is an alternative to primary surgery,” said principal investigator Sean Kehoe, MD, Lawson Tait Professor of Gynecological Cancer, University of Birmingham, UK. The first was the European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial.
Ovarian cancer is the most frequent cause of death from gynecological cancers. Symptoms are nonspecific, and over 60% of patients present with advanced disease. Only about 40% of patients are alive at 5 years, and better treatments are needed, he told listeners.
The MRC CHORUS trial enrolled 552 patients with stage III/IV ovarian cancer between March 2004 and August 2010. Of these, 276 were randomly assigned to primary debulking surgery followed by six cycles of platinum-based chemotherapy and 274 were randomly assigned to three cycles of neoadjuvant platinum-based chemotherapy followed by surgery and then another three cycles of chemotherapy.
Both arms had similar demographic and disease characteristics. Median age was 65.5 years, median tumor size was 8 cm, and 25% had stage IV disease. About 20% of patients in both arms had poor performance status (World Health Organization [WHO] performance status 2 or 3). About 79% of those in the primary surgery arm and 68% of those in the neoadjuvant arm had high-grade serous carcinoma.
Optimal debulking was possible in 16% of the primary surgery arm vs 40% of the neoadjuvant chemotherapy arm. Toxicity was greater in the primary surgery arm. Grade 3 or higher toxicity occurred in 48% vs 40%, respectively. Postoperative complications were higher as well, with grade 3 or 4 complications occurring in 24% vs 14%, respectively.
Hospital stay was shorter with neoadjuvant chemotherapy; 74% in the primary surgery arm were discharged within 14 days, compared with 92% treated with neoadjuvant chemotherapy arm. Fewer deaths within 28 days were reported with neoadjuvant chemotherapy: 14 (5.6%) in the primary surgery arm vs 1 (0.5%) in the neoadjuvant chemotherapy arm.
No significant difference in median progression-free survival was observed between the two arms (10.3 months for primary surgery vs 11.7 months for neoadjuvant chemotherapy). Median survival was 22.8 vs 24.5 months, respectively. ■
Disclosure: Dr. Kehoe reported no potential conflicts of interest.
1. Kehoe S, Hook J, Nankivell M, et al: Chemotherapy or upfront surgery for newly diagnosed advanced ovarian cancer: Results from the MRC CHORUS trial. 2013 ASCO Annual Meeting. Abstract 5500. Presented June 1, 2013.
The CHORUS trial had similar results to the previous European Organisation for Research and Treatment of Cancer (EORTC) 55971 study, showing noninferiority for primary debulking surgery followed by chemotherapy vs neoadjuvant chemotherapy followed by surgery and additional chemotherapy, said formal ...