Perspectives on Sequencing in Metastatic RCC

First-line therapy options in metastatic renal cell carcinoma (mRCC) include tyrosine kinase inhibitors (TKIs), and mammalian target of rapamycin (mTOR) inhibitors. When a TKI is appropriate, Bernard Escudier, MD, prefers to use axitinib, because it is the most active TKI in terms of tumor shrinkage; when an mTOR inhibitor is appropriate, he prefers everolimus.

In the second-line setting, Escudier again prefers everolimus or axitinib, depending on which one he used first-line. In terms of efficacy, the available evidence seems to indicate that everolimus has similar activity as compared with axitinib, he adds. In terms of adverse events, in general, less toxicities occur with agents when they are given after a TKI, compared with following cytokine therapy, says Escudier.

The RECORD-3 trial evaluated whether sequencing everolimus followed by sunitinib had a noninferior progression-free or overall survival, compared with the same two agents in reverse. The data supported the standard of care, which was first-line sunitinib followed by everolimus, notes Susanne Osanto, MD. There was no excess toxicity observed, she adds.

The RECORD-4 trial enrolled patients with clear cell mRCC following prior first-line therapy with sunitinib, another anti-vascular endothelial growth factor receptor agent, or a cytokine. The efficacy and safety of everolimus in the second-line setting was confirmed, says Osanto. The results did not vary depending on choice of first-line therapy, she adds.

In general, Osanto offers an mTOR inhibitor to all patients who fail first-line treatment. Patients, for whom she might instead choose a second-line TKI, include those with a diabetes mellitus diagnosis, a preexisting lung condition, or an immune deficiency.