Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with advanced ovarian cancer (MITO-7): a randomised, multicentre, open-label, phase 3 trial.

BACKGROUND: Carboplatin plus paclitaxel administered every 3 weeks is standard first-line chemotherapy for patients with advanced ovarian cancer. A weekly paclitaxel schedule combined with carboplatin every 3 weeks prolonged progression-free survival and overall survival in a Japanese phase 3 trial. The aim of our study was to assess whether a weekly schedule of carboplatin plus paclitaxel is more effective than the same drugs given every 3 weeks. METHODS: We did a multicentre, randomised, phase 3 study at 67 institutions in Italy and France. Women with FIGO stage IC-IV ovarian cancer, an ECOG performance status of 2 or lower, and who had never received chemotherapy were randomly allocated in a 1:1 ratio to receive either carboplatin (AUC 6 mg/mL per min) plus paclitaxel (175 mg/m(2)) every 3 weeks for six cycles or carboplatin (AUC 2 mg/mL per min) plus paclitaxel (60 mg/m(2)) every week for 18 weeks. Randomisation was done by computer-based minimisation, stratified by centre, residual disease after surgery, and ECOG performance status. The study was not blinded. Coprimary endpoints were progression-free survival and quality of life (assessed by the Functional Assessment of Cancer Therapy Ovarian Trial Outcome Index [FACT-O/TOI] score), and analysis was by modified intention to treat. This report presents the final analysis. The study is registered with ClinicalTrials.gov, number NCT00660842. FINDINGS: 822 patients were enrolled into the study between Nov 20, 2008, and March 1, 2012; 12 withdrew their consent immediately after randomisation and were excluded, and 810 were eligible for analysis. 404 women were allocated treatment every 3 weeks and 406 were assigned to the weekly schedule. After median follow-up of 22·3 months (IQR 16·2-30·9), 449 progression-free survival events were recorded. Median progression-free survival was 17·3 months (95% CI 15·2-20·2) in patients assigned to treatment every 3 weeks, versus 18·3 months (16·8-20·9) in women allocated to the weekly schedule (hazard ratio 0·96, 95% CI 0·80-1·16; p=0·66). FACT-O/TOI scores differed significantly between the two schedules (treatment-by-time interaction p<0·0001); with treatment every 3 weeks, FACT-O/TOI scores worsened at every cycle (weeks 1, 4, and 7), whereas for the weekly schedule, after transient worsening at week 1, FACT-O/TOI scores remained stable. Fewer patients assigned to the weekly group than those allocated treatment every 3 weeks had grade 3-4 neutropenia (167 [42%] of 399 patients vs 200 [50%] of 400 patients), febrile neutropenia (two [0·5%] vs 11 [3%]), grade 3-4 thrombocytopenia (four [1%] vs 27 [7%]), and grade 2 or worse neuropathy (24 [6%] vs 68 [17%]). Three deaths during the study were attributed to chemotherapy; two women died who were allocated treatment every 3 weeks and one death was recorded in the group assigned the weekly regimen. INTERPRETATION: A weekly regimen of carboplatin and paclitaxel might be a reasonable option for first-line treatment of women with advanced ovarian cancer. FUNDING: None.

The Promher Study: An Observational Italian Study on Adjuvant Therapy for HER2-Positive, pT1a-b pN0 Breast Cancer.

BACKGROUND: The management of pT1a-b pN0 HER2-positive breast cancer is controversial and no data about the efficacy of trastuzumab in this setting are available from randomized clinical trials. The aims of this retrospective study were to assess how patients are managed in clinical practice in Italy, which clinical or biological characteristics influenced the choice of adjuvant systemic therapy and the outcome of patients. METHODS: Data of consecutive patients who underwent surgery from January 2007 to December 2012 for HER2-positive, pT1a-b pN0 M0 breast cancer were retrospectively collected from 28 Italian centres. Analysis of contingency tables and multivariate generalized logit models were used to investigate the association between the baseline clinical and biological features and the treatment strategy adopted. RESULTS: Among 303 enrolled patients, 204 received adjuvant systemic therapy with trastuzumab, 65 adjuvant systemic therapy without trastuzumab and 34 did not receive adjuvant systemic therapy. At the multivariate analysis age, tumor size, proliferation index and hormone receptor status were significantly associated with the treatment choice. Five-year disease-free survival (DFS) probability was 95%, 94.3% and 69.6% for patients treated with adjuvant systemic therapy and trastuzumab, with adjuvant systemic therapy without trastuzumab and for patients who did not receive adjuvant systemic therapy, respectively (p<0.001). CONCLUSIONS: The majority of patients (66%) with pT1a-b pN0 HER2-positive breast cancer enrolled in this retrospective study received adjuvant systemic therapy with trastuzumab, whereas only 11% patients did not receive any adjuvant systemic therapy. It should be emphasized, however, that in the adjuvant systemic therapy without trastuzumab group 94% of tumors were hormone receptor positive and 89% of patients were treated with endocrine therapy only [corrected]. The 5-year DFS probability was significantly higher for patients receiving adjuvant systemic therapy with trastuzumab compared with patients not receiving adjuvant systemic therapy or receiving adjuvant systemic therapy without trastuzumab.