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Cabozantinib is safe and active in advanced non-clear cell renal cell carcinoma


Cabozantinib ( Cabometyx ) has shown robust clinical activity in advanced clear cell renal cell carcinoma ( RCC ).
Non-clear cell renal cell carcinoma ( nccRCC ), a heterogeneous mix of diseases, have been underrepresented in clinical trials and effective systemic therapy is lacking.

Researchers have retrospectively characterized the clinical activity and toxicity of Cabozantinib in non-clear cell renal cell carcinoma.

Medical records from advanced nccRCC patients treated with Cabozantinib across 18 institutions were reviewed.
Objective response rate ( ORR ) was assessed by RECIST. Clinical benefit ( CB ) included ORR or stable disease. Time to treatment failure ( TTF ) and overall survival ( OS ) were estimated by Kaplan-Meier.

Researchers have identified 80 patients with non-clear cell renal cell carcinoma: papillary ( 59% ), chromophobe ( 10% ), collecting duct ( 5% ), Xp11.2 translocation ( 15% ) or unclassified ( 11% ).

The majority were IMDC intermediate / poor risk ( 88% ) and received Cabozantinib greater than or equal to 3rd line ( 53% ).

Median exposure was 4 months ( range: less than 1-23 ). 48% remained on Cabozantinib while 42% had discontinued for progression and 5% for toxicity.

Most common adverse events were fatigue ( 51% ) and rash ( 33% ).

In 66 patients on Cabozantinib greater than or equal to 8 weeks, ORR was 27.3%. 71% had clinical benefit; with 64% durable clinical benefit greater than or equal to 6 months.

Median overall survival was 11 months ( 95% CI 9-NR ).

Time to treatment failure was 6.9 months ( 95% CI 4.8-9.9 ).

Most frequently altered genes in 43 patients with NGS were MET ( 21% ) and CDKN2A ( 19% ). Of the 7 evaluable papillary RCCs with MET alterations, 5 ( 71% ) achieved clinical benefit.

In conclusion, Cabozantinib is safe and active in non-clear cell renal cell carcinoma. ( Xagena )

Source: American Society of Clinical Oncology - ASCO Meeting, 2018

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