Axitinib (Inlyta®): A Comprehensive Oncological and Pharmacological Review

Executive Summary

Axitinib represents a significant advancement in the targeted therapy of advanced renal cell carcinoma (RCC). As a potent, second-generation, small-molecule inhibitor of vascular endothelial growth factor receptors (VEGFRs), it was developed to offer greater selectivity and potency over first-generation agents. Initially approved as a second-line monotherapy, its clinical utility was established in the pivotal Phase III AXIS trial, where it demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to sorafenib in patients who had failed one prior systemic therapy. This trial solidified Axitinib's role in the treatment algorithm for mRCC and validated PFS as a key regulatory endpoint in this setting.

The therapeutic landscape for RCC was subsequently revolutionized by the advent of immune checkpoint inhibitors (ICIs). Axitinib emerged as a premier combination partner, with landmark trials such as KEYNOTE-426 (with pembrolizumab) and JAVELIN Renal 101 (with avelumab) demonstrating superior overall survival (OS) and PFS for the combination regimens over sunitinib monotherapy in the first-line setting. These results established Axitinib-ICI combinations as a new standard of care. This enhanced efficacy, however, is associated with a more challenging toxicity profile, requiring careful patient selection and proactive management of adverse events.