Prognostic value of EndoPredict test in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative primary breast cancer screened for the randomized, double-blind, phase III UNIRAD trial.

BACKGROUND: The purpose of this study was to evaluate the prognostic value of the multigene EndoPredict test in prospectively collected data of patients screened for the randomized, double-blind, phase III UNIRAD trial, which evaluated the addition of everolimus to adjuvant endocrine therapy in high-risk, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. PATIENTS AND METHODS: Patients were classified into low or high risk according to the EPclin score, consisting of a 12-gene molecular score combined with tumor size and nodal status. Association of the EPclin score with disease-free survival (DFS) and distant metastasis-free survival (DMFS) was evaluated using Kaplan-Meier estimates. The independent prognostic added value of EPclin score was tested in a multivariate Cox model after adjusting on tumor characteristics. RESULTS: EndoPredict test results were available for 768 patients: 663 patients classified as EPclin high risk (EPCH) and 105 patients as EPclin low risk (EPCL). Median follow-up was 70 months (range 1-172 months). For the 429 EPCH randomized patients, there was no significant difference in DFS between treatment arms. The 60-month relapse rate for patients in the EPCL and EPCH groups was 0% and 7%, respectively. Hazard ratio (HR) supposing continuous EPclin score was 1.87 [95% confidence interval (CI) 1.4-2.5, P < 0.0001]. This prognostic effect remained significant when assessed in a Cox model adjusting on tumor size, number of positive nodes and tumor grade (HR 1.52, 95% CI 1.09-2.13, P = 0.0141). The 60-month DMFS for patients in the EPCL and EPCH groups was 100% and 94%, respectively (adjusted HR 8.10, 95% CI 1.1-59.1, P < 0.0001). CONCLUSIONS: The results confirm the value of EPclin score as an independent prognostic parameter in node-positive, hormone receptor-positive, HER2-negative early breast cancer patients receiving standard adjuvant treatment. EPclin score can be used to identify patients at higher risk of recurrence who may warrant additional systemic treatments.

The efficacy of a combination of ondansetron, methylprednisolone and metopimazine in patients previously uncontrolled with a dual antiemetic treatment in cisplatin-based chemotherapy. The French Ondansetron Study Group.

BACKGROUND: Cisplatin is one of the most effective cytotoxic drugs used in the treatment of certain neoplasms, but is also one which most frequently induces nausea and vomiting. Combination of corticosteroids with ondansetron enables greater control of emesis than that obtained with ondansetron alone, but some patients still experience symptoms. The objective of this randomised, double-blind, multicentre, parallel group study was to examine the benefit of the addition of metopimazine (MPZ), a dopamine receptor antagonist, to the combination of ondansetron + methylprednisolone (O + M) in the prevention of cisplatin-induced nausea and vomiting in patients uncontrolled [i.e., at least one emetic episode (vomiting and/or retching) or moderate or severe nausea] during their previous course of cisplatin based chemotherapy, despite antiemetic treatment with a combination of a 5-hydroxytryptamine3 receptor antagonist (5HT3) with a corticosteroid. The impact of the treatment on the patients' quality of life was also evaluated using two specific questionnaires the FLIC (Functional Living Index for Cancer), and the FLIE (Functional Living Index for Emesis). PATIENTS AND METHODS: The intent-to-treat population consisted of 338 patients; 168 patients received the triple combination of ondansetron, methylprednisolone and metopimazine (O + M + MPZ), and 170 patients received ondansetron plus methylprednisolone (O + M). Tumour type was comparable in the two treatment groups, the most prevalent being lung cancer. Patients in group O + M + MPZ received ondansetron as an 8 mg intravenous injection prior to chemotherapy on day 1 followed by 8 mg tablets b.i.d. from D2 to D3, methylprednisolone as a 120 mg intravenous injection prior to chemotherapy on D1 and followed by 16 mg tablets b.i.d. from D2 to D3, and metopimazine as a 40 mg intravenous injection prior to chemotherapy on D1 and followed by 15 mg capsules b.i.d. on D2 to D3. Patients in group O + M received treatment with ondansetron and methylprednisolone as above. RESULTS: Analysis of the primary efficacy criterion (absence of emetic episode throughout the course of chemotherapy) revealed a success rate of 53% in the group receiving O + M + MPZ and 38% in the group receiving O + M (P = 0.008). Analysis of the secondary efficacy criteria (nausea grade, number of emetic episodes and global patient satisfaction on D1 and from D2 to D3) showed a statistically significant difference between the two groups, in favour of the O + M + MPZ treatment. The scores obtained with the FLIC and FLIE questionnaires did not reveal any significant differences between the two groups. Treatment was well tolerated in both groups. CONCLUSION: The study showed that the addition of MPZ to the combination O + M was an effective and well tolerated antiemetic treatment, with a 15% increase in efficacy compared to the combination in patients not controlled during their previous course of chemotherapy. The addition of metopimazine to existing regimens containing 5HT3 receptor antagonist and steroid combination should be considered for patients who fail on their previous course.