Axitinib, is a selective, second generation tyrosine kinase inhibitor of VEGFRs.

A kinase inhibitor for the treatment of advanced renal cancer, after failure of one prior systemic therapy.

A second generation, selective inhibitor of VEGFR 1,2, and 3 that blocks VEGFRs at sub-namolar drug concentrations.

Relative potency 50-450 times greater than first generation VEGFR inhibitors.

Does not block PDGFR. BRAF, KIT, and FLT-3 as many first generation agents do.

A selective inhibitor of vascular endothelial growth factor.

An anti-angiogenesis agent, it inhibits receptor tyrosine kinases, including vascular endothelial growth factor receptors 1, 2 and 3 (VEGFR1,2,3).

Phase 2 study with cytokine refractory RCC objective response rate 44%, with a median time to progression 15.7 months and overall survival 29.9 months, and 5 year survival 20.6% (rixe O et al).

In a randomized, open labeled clinical study of 723 patients whose disease progressed on or after treatment with one prior systemic therapy: Median progression free survival was 6.7 months in those treated with axitinib, compared with 4.7 months in those treated with sorafenib.

Axitinib 5 mg twice a day in the second line setting has a greater objective response compared with sorafenib 400 mg twice daily.

In a phase III trial comparing axitinib with sorafenib, the most benefit was seen in cytokine refractory patients, while in patients with prior sunitinib treatment with a delay in progression of 1.4 months.

Oral agent administered 5 mg b.i.d.

Initial dosing 5mg bid, titrated up to 7mg bid, and up to 10mg bid.

Should not be concurrently with CYP3A4/5 inducers.

Marketed as Inlyta.

Is a treatment option for unresectable and metastatic carcinoid tumors.

The 12 month progression-free survival (PFS)] rate associated with axitinib in advanced carcinoid tumors is promising when compared to results observed in phase 2 studies of other antiangiogenic TKIs such as sunitinib or pazopanib.

5 mg, twice daily in metastatic carcinoid was associated with a PFS rate of 65% at 12 months, ans a 1-year overall survival (OS) rate of 93%.

Associated with a 90% hypertension rate in the above study, with grade 3 hypertension occurring in 60% of study participants, and grade 4 hypertension being observed in 7% of patients.

Most common side effects occurring in more than 20% of patients are diarrhea, hypertension, fatigue, anorexia, nausea, dysphonia, hand-foot syndrome, weight loss, vomiting, asthenia, and constipation.

Blood pressure should be controlled before start of treatment and should be monitored during therapy.

In combination with pembrolizumab in advanced renal cell carcinoma in treatment naive patients the response rate was 73% and median progression free survival exceeded 20 months.

Axitinib with Pembrolizumab in advanced renal carcinoma resulted in significantly longer overall survival and progression free survival and a high response rate in treatment with sunitinib (Rini B).

Axitinib combined with Avelumab resulted in a significantly longer progression free survival among patients with sunitinib for first line treatment of advanced renal cancer.

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