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21-01-2019 | Kidney cancer | News | Article

Sustained benefit of VEGFR–TKIs after doublet immunotherapy in metastatic RCC

medwireNews: Second-line treatment with vascular endothelial growth factor receptor–tyrosine kinase inhibitors (VEGFR–TKIs) after failure of nivolumab plus ipilimumab continues to benefit patients with metastatic renal cell carcinoma (RCC), report researchers.

Following the results of the CheckMate 214 trial showing an overall survival (OS) advantage with the combination of nivolumab and ipilimumab over sunitinib in treatment-naïve patients with an intermediate- or poor-risk prognosis, the combination has been approved for this indication by the US FDA, they explain.

The investigators add that in line with “the changing paradigm” of first-line therapy in these patients, “the subsequent treatment algorithm needs to be redefined.”

Laurence Albiges, from Gustave Roussy in Villejuif, France, and team therefore evaluated the outcomes of 33 participants of the nivolumab–ipilimumab arm of the CheckMate 214 trial who subsequently received VEGFR–TKIs, most commonly sunitinib (51.5%), followed by axitinib (24.2%), pazopanib (18.2%), and cabozantinib (6.1%).

Over a median follow-up of 22 months from the initiation of TKI therapy, 36% of patients attained an objective response (all partial responses), while 39% had stable disease, which gave a disease control rate of 75%.

Median progression-free survival was 8 months, with no significant difference between individuals who received first-generation (sunitinib or pazopanib) or second-generation (axitinib or cabozantinib) TKIs, and the 12- and 24-month OS rates were 54% and 37%, respectively.

These results suggest “a sustained benefit of VEGFR TKIs after immune checkpoint doublet,” say the study authors, with the response and clinical benefit rates aligned with those of the historical registration trials of first-line VEGFR–TKIs.

They add however that “the optimal sequence is yet to be defined,” and hope that trials such as the phase II SUAVE study comparing the sequence of avelumab–sunitinib with sunitinib–avelumab will help answer this question.

The team reports in the European Journal of Cancer that the safety profile was “as expected.” Adverse events of grade 3 or worse occurred in 42% of patients, most commonly hand–foot syndrome in 9%, followed by high blood pressure, pulmonary embolism, diarrhea, and infections in 6% of patients each.

By Shreeya Nanda

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