The PI3K inhibitor member Buparlisib codenamed BKM120, although not yet available, has been explored therapeutically in many tumors. In phase I clinical studies, Buparlisib demonstrated some control in advanced solid tumors, including breast cancer.
This article takes a look at what role Buparlisib has in advanced breast cancer that is resistant to anti HER2 -targeted therapy.
Theoretical basis for the PI3K inhibitor mechanism
Buparlisib is a new drug called a “PI3K inhibitor” that works by acting on the “PI3K/Akt/mTOR signaling pathway” in tumor cells.
The activation of many malignancies is associated with the PI3K/Akt/mTOR signaling pathway. When PI3K s inhibition fails in vivo, stimulatory signaling is activated and tumorigenesis is much more likely.
In breast cancer, activation of the PI3K/Akt/mTOR signaling pathway is up to 70%. Theoretically, it may be possible to control breast cancer by blocking PI3K/Akt/mTOR signaling pathway activation with PI3K inhibitors.
After targeted therapy resistance, is the combination of Buparlisib effective?
In a small study, 17 patients with HER2 positive locally advanced or metastatic breast cancer were added with Buparlisib after trastuzumab (Trastuzumab) treatment failure. as a result, disease control was 75%, with 17% of patients achieved partial remission, and 58% of patients had stable disease for more than 1½ months. Major adverse events during treatment included rash, hyperglycemia, and diarrhea.
In another study, 24 patients with advanced HER2-positive breast cancer were treated with lapatinib in combination with buparlisib after drug resistance and achieved a disease control rate of 79%, with 1 patient in complete remission and 6 patients with stable disease for more than half a year. Major side effects include diarrhea, nausea, rash, malaise, and depression.
For HER2 positive advanced breast cancer, supplemental Buparlisib may still work after conventional anti-HER2 targeted therapy has failed, but this option needs to be validated in more rigorous clinical studies and there is a long way to go.
More to explore
More research on Buparlisib in breast cancer is ongoing, including exploring its use in endocrine-therapy-resistant hormone receptor-positive advanced breast cancer, in combination with chemotherapy drugs for metastatic breast cancer, in addition to triple-negative breast cancer, which is also a direction of interest for investigators.
Desirably, studies on Buparlisib have also been conducted in our population.The study of Buparlisib in advanced solid tumors such as breast cancer has been concluded, but the results are not yet available (CTR20130853).
Summary
HER2 positive advanced breast cancer may have the opportunity to use Buparlisib to counteract drug resistance and further control tumor progression, but the evidence for this remains insufficient.Adverse effects such as elevated transaminases, hyperglycemia, nausea, fatigue, diarrhea, rash, and mood abnormalities may occur during Buparlisib treatment.
More studies on Buparlisib in breast cancer are ongoing, and we look forward to more data to surprise us.