However, despite all these studies supporting the development of HDIs for clinical use, no superiority of these agents over conventional antineoplastic agents has yet been directly proven.
All Phase III studies with sunitinib (angiogenesis inhibitor), 21 linifanib (angiogenesis kinase inhibitor), 22 and brivanib (inhibitor of VEGF and FGF receptors) 23 failed in demonstrating superiority of these agents over sorafenib.
The legitimate question arises: could the early superiority of new agents identified in the stage IV setting signal a future potential curative effect if used in the adjuvant setting?
The superiority of AI agents over tamoxifen for the treatment of postmenopausal women with advanced breast cancer [ 6, 12] and also over the combination of an AI plus tamoxifen in the adjuvant setting [ 7], has indeed been confirmed in several key clinical trials.
The use of non-calcium-containing phosphate binders is preferable, according to KDIGO guidelines [ 91], although a recent systematic review did not find sufficient evidence to confirm the superiority of these agents over calcium-based binders for CV end-points [ 92].
As the superiority of one agent over the other remains unclear, we designed a systematic review and meta-analysis of these agents in patients with ACS undergoing PCI.
Lack of head to head comparisons of available treatment options limits conclusions regarding superiority of one agent over another in improving QoL in psoriasis patients.
The relative cost of antifungal therapies has become an increasingly important issue in recent years due to growing concerns about the rising costs of healthcare and the lack of data demonstrating the superiority of one agent over another [ 26].
Such indirect comparisons of continuation rates however are insufficient for accepting the superiority of one agent over another only direct comparisons, such as in our trial, can answer this question with confidence.
The superiority of new cytotoxic agents incorporated into the preoperative systemic therapy has not been definitely confirmed.
However, to date there is no evidence of the superiority of any chemotherapeutic agent alone or of monotherapy versus combination therapy in TACE [111, 112].
