Buparlisib Demonstrates Preliminary Activity in VEGF-refractory mRCC

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Buparlisib at a dose of 80 mg/day in combination with bevacizumab was a tolerable and demonstrated preliminary activity.
Buparlisib at a dose of 80 mg/day in combination with bevacizumab was a tolerable and demonstrated preliminary activity.

Buparlisib at a dose of 80 mg/day in combination with bevacizumab was a tolerable and demonstrated preliminary activity in patients with vascular growth factor (VEGF)-refractory metastatic renal cell carcinoma (mRCC), a study published in Cancer has shown.1

Because the phosphatidylinositol-3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is dysregulated in patients with mRCC, researchers sought to evaluate the tolerability and activity of buparlisib, a pan-PI3K inhibitor, with bevacizumab in mRCC. Their objective was also to determine the maximum tolerated dose and dose-limiting toxicities of the combination.

For the phase 1 trial, researchers enrolled 32 patients with mRCC who were refractory to prior anti-VEGF therapy. A total of 87% had clear cell histology and half received 2 or more prior lines of therapy. Participants received buparlisib at a dose of 60, 80, or 100 mg orally per day plus bevacizumab 10 mg/kg intravenously every 2 weeks.

Investigators determined the maximum tolerated dose of buparlisib to be 80 mg/day with bevacizumab.

Researchers found that 28 patients discontinued therapy: 17 due to disease progression, 7 because of toxicity, and 4 for other reasons. Dose-limiting toxicities included rash, pruritis, elevated lipase, elevated amylase, anorexia, and psychiatric disorders.

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In regard to efficacy, of the 30 evaluable patients, 13% (95% CI, 4-31) achieved a partial response. Of note, 2 patients who harbored activating PI3KA mutations experienced 42% and 16% maximal tumor shrinkage, respectively.

The findings ultimately suggest that further trials evaluating this combination are warranted for patients with mRCC, particularly those with activating PI3KA mutations.

Reference

  1. McKay RR, De Velasco G, Werner L, et al. A phase 1 study of buparlisib and bevacizumab in patients with metastatic renal cell carcinoma progressing on vascular endothelial growth factor-targeted therapies [published online ahead of print May 19, 2016]. Cancer. doi: 10.1002/cncr.30056.

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