Patients with advanced ovarian cancer have similar survival outcomes thus far with a weekly regimen of carboplatin/paclitaxel vs the standard every-3-week regimen, but the weekly regimen is much better tolerated with improved quality of life, according to final results of the Multicenter Italian Trials in Ovarian Cancer (MITO)-7 randomized, controlled, phase III study.1
“Progression-free survival was only 2 months longer with the weekly regimen, which was not statistically significant, but all quality-of-life measures significantly favored weekly treatment,” said presenting author Sandro Pignata, MD, PhD, National Cancer Institute, Naples, Italy. “These results support a weekly regimen as first-line treatment for advanced ovarian cancer.”
MITO-7 was based on a previous trial by Japanese investigators showing significantly longer progression-free and overall survival with weekly paclitaxel combined with every-3-week carboplatin vs standard carboplatin/paclitaxel given every 3 weeks.2
The study randomly assigned 822 patients with stage IC through IV ovarian cancer to receive carboplatin/paclitaxel (carboplatin AUC6 plus paclitaxel 175 mg/m2 on day 1) every 3 weeks for six cycles vs weekly carboplatin/paclitaxel (carboplatin AUC2 plus paclitaxel 60 mg/m2) for 18 consecutive administrations.
The final analysis was conducted March 2013 at a median follow-up of 20 months and included 808 patients. Both treatment arms were well balanced for baseline characteristics. Median age was 60 years, 75% were Eastern Cooperative Oncology Group (ECOG) performance status 0, 85% were stage III or IV, and compliance was good in both arms.
Progression-free survival was slightly—but not significantly—longer with the weekly regimen (18.8 vs 16.5 months). The main prognostic factors associated with progression-free survival were disease stage and residual disease. No interaction was observed between treatment arm and main prognostic factors, including age, stage, and size of institution. Overall survival data are not yet mature.
Quality of life was assessed for the first three cycles of chemotherapy using the Functional Assessment of Cancer Therapy (FACT)-Ovarian scale and the FACT/Gynecologic Oncology Group (GOG)-Neurotoxicity (Ntx) subscale. For all scales, quality of life significantly favored the weekly arm (P < .0001). For patients randomized to the every-3-week regimen, quality of life worsened 1 week after each course, but quality of life remained stable throughout treatment in the weekly arm after a slight dip following week 1.
The weekly arm had significantly less severe neutropenia, febrile neutropenia, thrombocytopenia, renal toxicity, and neuropathy. Significantly less hair loss, neuropathy, and vomiting were also reported in the weekly arm.
An audience member questioned whether platinum and paclitaxel were underdosed in the weekly arm, but Dr. Pignata said there was no evidence for that. “The Japanese trial was designed to be dose-dense. But if we look at the number of patients that completed six cycles in MITO-7, this was much higher than in the Japanese trial,” he noted. ■
Disclosure: Dr. Pignata reported no potential conflicts of interest.
1. Pignata S, Scambia G, Lauria R, et al: A randomized multicenter phase III study comparing weekly versus every 3 weeks carboplatin plus paclitaxel in patients with advanced ovarian cancer: Multicenter Italian Trials in Ovarian Cancer (MITO)-7—European Network of Gynaecological Trial Groups (ENGOT-ov-10) and Gynaecologic Cancer Intergroup (GCIG) trial. 2013 ASCO Annual Meeting. Abstract LBA5501. Presented June 1, 2013.
2. Katsumata N, Yasuda M, Takahashi F, et al: Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: A phase 3, open-label, randomised controlled trial. Lancet 374:1331-1338, 2009.
Weekly vs every-3-week therapy is a somewhat controversial area in ovarian cancer, said formal discussant of the MITO-7 trial, Jonathan S. Berek, MD, Director of the Stanford Women’s Cancer Center, Palo Alto, California.
“[Japan Clinical Oncology Group (JCOG)]-16 showed a survival advantage for...