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allied
academies
J Med Oncl Ther 2017 | Volume 2 Issue 3
Breast Cancer
November 01-02, 2017 | Toronto, Canada
7
th
World Congress on
Background:
Phosphatidylinositol-3-kinase (PI3K) and
androgen receptor pathway activation is common in
metastatic castration resistant prostate cancer (mCRPC).
Buparlisib is an oral, pan-class I PI3 kinase inhibitor.
Methods:
This was a multisite single arm phase II trial of
buparlisib 100 mg ± enzalutamide daily in men with mCRPC
whose disease progressed on or who were not candidates
for docetaxel. The primary end-point was the rate of
radiographic/clinical progression-free survival (PFS) at 6
months.
Results:
Thirty men were accrued: 67% post-docetaxel;
median prostate specific antigen (PSA) was 70 ng/dl, 83%
had ≥4 prior therapies for mCRPC; 43% received concurrent
enzalutamide. The final 6 month PFS rate was estimated
to be 10% (95% confidence interval 2.5–23.6%). Median
PFS was 1.9 months and was 3.5 months with concurrent
enzalutamide. Median overall survival was 10.6 months.
Concurrent enzalutamide led to a five-fold reduction in
buparlisib concentrations. PSA declines were observed
in 23%; no patients achieved a ≥50% decline, and no
radiographic responses were observed. Severe adverse
events occurred in four men including respiratory infection
and multi-organ failure, urinary tract obstruction, confusion
and one seizure in the setting of a new central nervous
system (CNS) metastasis. Grade III adverse events were
seen in 43% of patients; common toxicities included grade
I–II weight loss, diarrhoea, nausea, fatigue, anorexia, rash,
hyperglycemia and anxiety/mood disorders.
Conclusions:
Buparlisib did not demonstrate significant
activity in men with mCRPC, suggesting that PI3K inhibition
is not sufficient to reverse resistant mCRPC progression.
Future studies of PI3K pathway inhibitors with concurrent
enzalutamide should develop optimal dosing and focus on
selected patients more likely to benefit.
Phase II trial of the PI3 kinase inhibitor buparlisib (BKM-120) with or without enzalutamide in men
with metastatic castration resistant prostate cancer
Livingstone Semukaya
Save A Life Foundation, Uganda