In a phase 2 study, bosutinib, an oral drug approved for treating certain cases of chronic myeloid leukemia, slowed cyst growth in patients with autosomal dominant polycystic kidney disease (ADPKD).

In the 2-year placebo-controlled study, patients treated with bosutinib 200 mg/day experienced a significant 66% reduction in the annual rate of kidney enlargement compared with placebo recipients (1.63% vs 4.74%).

The change in median kidney volume from baseline to end of treatment was about 100 mL smaller in the bosutinib 200 mg/day group compared with placebo recipients (62.7 vs 168.1 mL), researchers reported online ahead of print in the Journal of the American Society of Nephrology.

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The pathogenesis of ADPKD has been linked to overactivation of Src, and bosutinib is a dual Src/Bcr-Abl tyrosine kinase inhibitor, noted a research team led by Vladimir Tesar, PhD, of Charles University and General University Hospital in Prague, Czech Republic.

“The study offers evidence that Src kinase inhibitors may have the potential to retard the growth of cysts and kidney volume in ADPKD but the long-term benefit remains to be determined,” the researchers concluded.

Dr Tesar and his colleagues enrolled 172 patients with ADPKD. Of these, 169 receive at least 1 study dose. The study consisted of 4 groups. 58 patients who received bosutinib 200 mg/day; 31 who received bosutinib 400 mg/day; 24 who initially received bosutinib 400 mg/day but were later switched to 200 mg/day (400/200 mg/day group), and 56 who received placebo.

When the investigators compared pooled bosutinib results with placebo, the annual rate of kidney enlargement was reduced by 82% (0.84% vs 4.74%). The researchers observed no significant change in estimated glomerular filtration rate (eGFR) between the study arms during the treatment period.

The most frequent toxicities were gastrointestinal (GI) and liver-related adverse events (AEs), but the overall GI and liver toxicity profile was consistent with the profile demonstrated in previous studies of bosutinib. The researchers identified no new toxicities.

“Additional studies are needed to determine if gastrointestinal AEs leading to volume depletion increase risk of kidney injury,” the authors wrote. “Dose reductions and continued monitoring or limited use of bosutinib may be required to mitigate the occurrence of these AEs and prevent adverse effects on the kidney.”

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Tesar V, Ciechanowski K, Pei Y, et al. Bosutinib versus placebo for autosomal dominant polycystic kidney disease. J Am Soc Nephrology 2017; published online ahead of print.