A phase 2 trial of buparlisib in patients with platinum-resistant metastatic urothelial carcinoma.
Victor McPhersonBrendan ReardonAravind BhayankaraSasinya N ScottMariel E BoydIlana R Garcia-GrossmanAshley M RegazziAsia S McCoyPhilip H KimHikmat Al-AhmadieIrina OstrovnayaAndrew J RothAzeez FarookiMichael F BergerJonathan E RosenbergDavid B SolitEliezer Van AllenMatthew I MilowskyDean F BajorinGopakumar V IyerPublished in: Cancer (2020)
The phosphatidyl 3-inositol kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway frequently is upregulated in patients with metastatic urothelial carcinoma (UC). This trial explored buparlisib, an inhibitor of the pathway, in patients with heavily pretreated metastatic UC. Although the drug was found to have modest efficacy, with 6 patients experiencing stable disease and 1 patient achieving a partial response at 8 weeks on therapy, significant side effects also were observed. Patients with specific genetic alterations responded to treatment. Further studies of PI3K pathway inhibition are warranted using newer agents that have superior toxicity profiles and are more selective inhibitors of the pathway.
Keyphrases
- pi k akt
- signaling pathway
- cell proliferation
- squamous cell carcinoma
- small cell lung cancer
- end stage renal disease
- cell cycle arrest
- ejection fraction
- newly diagnosed
- clinical trial
- epithelial mesenchymal transition
- prognostic factors
- oxidative stress
- stem cells
- phase iii
- randomized controlled trial
- emergency department
- patient reported outcomes
- open label
- mesenchymal stem cells
- patient reported