Same Progression-Free Survival, Better Quality of Life With Lower-Dose Weekly vs Every-3-Week Carboplatin/Paclitaxel in Advanced Ovarian Cancer
In an open-label phase III trial (MITO-7) reported in The Lancet Oncology, Pignata et al found that while a lower-dose weekly carboplatin/paclitaxel regimen did not improve progression-free survival compared with standard every-3-week carboplatin/paclitaxel as first-line treatment of advanced ovarian cancer, it appeared to be associated with better quality-of-life outcomes and less severe toxicity.
Study Details
In the trial, conducted at 67 institutions in Italy and France, women with International Federation of Gynecology and Obstetrics (FIGO) stage IC to IV ovarian cancer who had received no prior chemotherapy were randomly assigned between November 2008 and March 2012 to receive carboplatin at AUC 6 mg/mL/min plus paclitaxel at 175 mg/m² every 3 weeks for six cycles (n = 404) or carboplatin at AUC 2 mg/mL/min plus paclitaxel at 60 mg/m² every week for 18 weeks (n = 406). Randomization was stratified by center, residual disease after surgery, and Eastern Cooperative Oncology Group (ECOG) performance status.
The coprimary endpoints were progression-free survival and quality of life assessed by scoring on the Functional Assessment of Cancer Therapy Ovarian Trial Outcome Index (FACT-O/TOI) over the first 9 weeks of treatment. This scale combines the physical and functional well-being and ovarian cancer–specific subscales of FACT-O, which has additional subscales for social and emotional outcomes. Analysis was by modified intention to treat.
The weekly treatment group and the every-3-week treatment group were generally balanced for age (median, 60 and 59 years), FIGO stage (IC in 8% and 6%, II in 8% in both, III in 58% and 63%, IV in 27% and 23%), primary tumor site (ovarian in 91%, peritoneal in 5%, fallopian tube in 4% in both), histology (eg, serous in 67% and 72%, endometrioid in 12% and 8%, clear cell in 5% and 6%, undifferentiated in 6% in both), tumor grade (G3 in 66% and 71%, G2 in 11% and 8%, G1 in 4% and 3%), ECOG performance status (0 in 74% and 75%, 1 in 23% and 22%, 2 in 3% in both), and residual disease (none in 41% in both, ≤ 1 cm in 12% in both, > 1 cm in 23% in both, no surgery in 24% and 25%).
No Difference in Progression-Free Survival
After a median follow-up of 22.3 months, median progression-free survival was 18.3 months in the weekly group vs 17.3 months in the every-3-week group (hazard ratio [HR] = 0.96, P = .66). The difference between treatments was unchanged on multivariate analysis adjusting for FIGO stage, ECOG performance status, residual disease, age, and size of the institution (HR = 0.94, P = .53). Residual disease and FIGO stage were independent predictors of progression-free survival.
In patients evaluable for tumor response, response rates were 56% in the weekly group (including 23 complete responses) and 59% in the every-3-week group (including 35 compete responses) (P = .63). Estimated overall survival at 24 months was 77.3% in the weekly group and 78.9% in the every-3-week group (HR = 1.20, P = .22), with the difference between treatments being unchanged on multivariate analysis (HR = 1.21, P = .21).
Quality of Life
Valid baseline quality-of-life questionnaires were completed by 75% of patients, consisting of 308 in the weekly group and 301 in the every-3-week group. In the every-3-week group, FACT-O/TOI scores worsened after every chemotherapy cycle (ie, at weeks 1, 4, and 7), whereas scores remained stable in the every-week group after a transient worsening at week 1. Treatment-by-time interaction was significant in favor of the weekly group (P < .0001). Similar outcomes were observed for the total FACT-O, FACT/Gynecologic Oncology Group-neurotoxicity module, and the neurotoxicity subscale (treatment-by-time interaction favoring weekly treatment, P < .0001 for all).
Toxicity
The weekly group had lower rates of grade 3 or 4 neutropenia (42% vs 50%), febrile neutropenia (0.5% vs 3%), grade 3 or 4 thrombocytopenia (1% vs 7%), grade ≥ 2 neuropathy (6% vs 17%), and grade 2 hair loss (29% vs 59%). Pulmonary toxic effects of any grade were more common in the weekly group (8.5% vs 4.5%). Three deaths were considered related to study treatment, consisting of two in the every-3-week group due to bowel perforation and febrile neutropenia and one in the weekly group due to bowel perforation.
The investigators concluded, “[C]arboplatin and paclitaxel given once a week compared with the standard regimen administered every 3 weeks did not significantly prolong progression-free survival in women with ovarian cancer, but it was associated with better quality of life and fewer toxic effects. On the basis of these data, we believe that a weekly schedule might be a reasonable alternative for first-line treatment of advanced ovarian cancer in clinical practice.”
Sandro Pignata, MD, of the Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione G Pascale, Naples, is the corresponding author for The Lancet Oncology article.
MITO-7 is an academic, nonprofit trial promoted by the National Cancer Institute of Napoli (NCI-NAP), Italy. Institutions at NCI-NAP are supported by the nonprofit charity Associazione Italiana per la Ricerca sul Cancro. The study authors reported no potential conflicts of interest.
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