Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation.

AIM: MERiDiAN evaluated plasma vascular endothelial growth factor-A (pVEGF-A) prospectively as a predictive biomarker for bevacizumab efficacy in metastatic breast cancer (mBC). METHODS: In this double-blind placebo-controlled randomised phase III trial, eligible patients had HER2-negative mBC previously untreated with chemotherapy. pVEGF-A was measured before randomisation to paclitaxel 90 mg/m2 on days 1, 8 and 15 with either placebo or bevacizumab 10 mg/kg on days 1 and 15, repeated every 4 weeks until disease progression, unacceptable toxicity or consent withdrawal. Stratification factors were baseline pVEGF-A, prior adjuvant chemotherapy, hormone receptor status and geographic region. Co-primary end-points were investigator-assessed progression-free survival (PFS) in the intent-to-treat and pVEGF-Ahigh populations. RESULTS: Of 481 patients randomised (242 placebo-paclitaxel; 239 bevacizumab-paclitaxel), 471 received study treatment. The stratified PFS hazard ratio was 0.68 (99% confidence interval, 0.51-0.91; log-rank p = 0.0007) in the intent-to-treat population (median 8.8 months with placebo-paclitaxel versus 11.0 months with bevacizumab-paclitaxel) and 0.64 (96% confidence interval, 0.47-0.88; log-rank p = 0.0038) in the pVEGF-Ahigh subgroup. The PFS treatment-by-VEGF-A interaction p value (secondary end-point) was 0.4619. Bevacizumab was associated with increased incidences of bleeding (all grades: 45% versus 27% with placebo), neutropenia (all grades: 39% versus 29%; grade ≥3: 25% versus 13%) and hypertension (all grades: 31% versus 13%; grade ≥3: 11% versus 4%). CONCLUSION: The significant PFS improvement with bevacizumab is consistent with previous placebo-controlled first-line trials in mBC. Results do not support using baseline pVEGF-A to identify patients benefitting most from bevacizumab. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT01663727.

Imatinib mesylate as treatment for adenoid cystic carcinoma of the salivary glands: report of two successfully treated cases.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a malignant neoplasia of the salivary glands that is treated primarily by surgery. Local control and survival are usually compromised despite surgery. Expression of KIT tyrosine kinase is involved in the pathogenesis of ACC. Imatinib mesylate is a potent inhibitor of KIT tyrosine kinase, so we explored the possibility that ACC could be a potential target for this drug. METHODS: We report two cases of unresectable ACC treated with imatinib mesylate in the context of recurrent disease (case 1) and locally advanced tumor at its initial presentation (case 2). RESULTS: Both patients responded well to treatment with imatinib mesylate. Significant regression of recurrent disease (case 1) resulted in a successful salvage surgical resection; the locally advanced tumor (case 2) had an excellent response to treatment, but, unfortunately, the patient refused salvage resection. CONCLUSION: This is the first time ACC is reported to respond to imatinib mesylate. Studies in which more patients are enrolled in controlled clinical trials are needed to confirm this observation.