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Combining TKIs and Immune Checkpoint Inhibitors in Advanced Kidney Cancer

By: Sarah Campen, PharmD
Posted: Monday, November 5, 2018

Advanced renal cell carcinoma is often managed with tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors as monotherapy. Recent studies combining these two therapeutic strategies have demonstrated “promising” efficacy with manageable toxicity profiles. The results and challenges with the combination therapy are highlighted in an editorial by oncologists Chung-Han Lee, MD, PhD, and Robert Motzer, MD, both of Memorial Sloan Kettering Cancer Center in New York, published in the British Journal of Cancer.

In a phase Ib trial that investigated the combination of axitinib and pembrolizumab in patients with advanced renal cell carcinoma, a partial or complete response was achieved in 73% of patients. As for toxicity, 65% of patients experienced a grade 3 or worse treatment-related adverse event, “consistent with single agent TKI therapy.”

Several other TKI/immunotherapy combinations, including atezolizumab/bevacizumab, avelumab/axitinib, and lenvatinib/pembrolizumab, also showed activity. A phase Ib/II trial assessing lenvatinib in combination with pembrolizumab reported an objective response rate in treatment-naive patients and all patients of 83% and 63%, respectively. In total, 60% of participants experienced a treatment-emergent adverse event.

Early clinical trials combining TKIs that inhibit VEGF receptors and immune checkpoint inhibitors reported activity, but the proportion of patients experiencing high-grade toxicity discouraged further development of the combination therapy. Although subsequent combinations of newer TKIs with immune checkpoint inhibitors have shown improved toxicity profiles, safety still remains a concern. “Until head-to-head trials of these combinations can be performed to compare their efficacy, biomarker development will be critical for patient stratification,” advised Drs. Lee and Motzer.



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