No abstract

The risk of venous thromboembolism (VTE) is increased in cancer patients. To improve prediction of VTE in cancer patients, we performed a prospective and observational cohort study of patients with newly diagnosed cancer or progression of disease after remission. A previously developed risk scoring model for prediction of VTE that included clinical (tumor entity and body mass index) and laboratory (hemoglobin level and thrombocyte and leukocyte count) parameters was expanded by incorporating 2 biomarkers, soluble P-selectin, and D-Dimer. Of 819 patients 61 (7.4%) experienced VTE during a median follow-up of 656 days. The cumulative VTE probability in the original risk model after 6 months was 17.7% in patients with the highest risk score (> 3, n ‫؍‬ 93), 9.6% in those with score 2 (n ‫؍‬ 221), 3.8% in those with score 1 (n ‫؍‬ 229), and 1.5% in those with score 0 (n ‫؍‬ 276). In the expanded risk model, the cumulative VTE probability after 6 months in patients with the highest

The value of any new therapeutic strategy or treatment is determined by the magnitude of its clinical benefit balanced against its cost. Evidence for clinical benefit from new treatment options is derived from clinical research, in particular phase III randomised trials, which generate unbiased data regarding the efficacy, benefit and safety of new therapeutic approaches. To date, there is no standard tool for grading the magnitude of clinical benefit of cancer therapies, which may range from trivial (median progression-free survival advantage of only a few weeks) to substantial (improved long-term survival). Indeed, in the absence of a standardised approach for grading the magnitude of clinical benefit, conclusions and recommendations derived from studies are often hotly disputed and very modest incremental advances have often been presented, discussed and promoted as major advances or 'breakthroughs'. Recognising the importance of presenting clear and unbiased statements regarding the magnitude of the clinical benefit from new therapeutic approaches derived from high-quality clinical trials, the European Society for Medical Oncology (ESMO) has developed a validated and reproducible tool to assess the magnitude of clinical benefit for cancer medicines, the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS). This tool uses a rational, structured and consistent approach to derive a relative ranking of the magnitude of clinically meaningful benefit that can be expected from a new anti-cancer treatment. The ESMO-MCBS is an important first step to the critical public policy issue of value in cancer care, helping to frame the appropriate use of limited public and personal resources to deliver cost-effective and affordable cancer care. The ESMO-MCBS will be a dynamic tool and its criteria will be revised on a regular basis.

We report the efficacy and safety of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) combination therapy in BRAF V600E-mutated anaplastic thyroid cancer, a rare, aggressive, and highly lethal malignancy with poor patient outcomes and no systemic therapies with clinical benefit. MethodsIn this phase II, open-label trial, patients with predefined BRAF V600E-mutated malignancies received dabrafenib 150 mg twice daily and trametinib 2 mg once daily until unacceptable toxicity, disease progression, or death. The primary end point was investigator-assessed overall response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety. ResultsSixteen patients with BRAF V600E-mutated anaplastic thyroid cancer were evaluable (median follow-up, 47 weeks; range, 4 to 120 weeks). All patients had received prior radiation treatment and/or surgery, and six had received prior systemic therapy. The confirmed overall response rate was 69% (11 of 16; 95% CI, 41% to 89%), with seven ongoing responses. Median duration of response, progression-free survival, and overall survival were not reached as a result of a lack of events, with 12-month estimates of 90%, 79%, and 80%, respectively. The safety population was composed of 100 patients who were enrolled with seven rare tumor histologies. Common adverse events were fatigue (38%), pyrexia (37%), and nausea (35%). No new safety signals were detected. ConclusionDabrafenib plus trametinib is the first regimen demonstrated to have robust clinical activity in BRAF V600E-mutated anaplastic thyroid cancer and was well tolerated. These findings represent a meaningful therapeutic advance for this orphan disease.