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Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Phase II study of BKM120 in patients with advanced esophageal squamous cell carcinoma (EPOC1303)
Takashi Kojima1, Ken Kato2, Hiroki Hara3
1Department of Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Background:
PI3K/AKT/mTOR pathway is frequently overactive in esophageal squamous cell carcinoma (ESCC), making it an attractive treatment target. BKM120 is an oral pan-class I PI3K inhibitor with promising activity in several cancers. We prospectively investigated efficacy, safety, and biomarkers of BKM120 in advanced ESCC. We conducted a multicenter phase II study of BKM120 monotherapy in patients with pretreated advanced ESCC.
Methods:
BKM120 (100 mg/day) was administered orally in a 28-day cycle. The primary end point was disease control rate (DCR). Tumor samples for all patients were collected for gene alteration analysis in a comprehensive genomic profiling assay.
Results:
Of 42 patients enrolled, 20 had stable disease and two had confirmed partial response. One ineligible patient was excluded from the primary analysis, which met the primary end point (DCR 51.2%; 95% confidence interval [CI], 35.1-67.1). In the 42 patients, median progression-free survival and overall survival were 2.3 (95% CI 1.8-3.2) and 9.0 (95% CI 6.5-11.4) months, respectively. Common grade 3 or 4 adverse events were rash, anorexia, hyponatremia, and abnormal hepatic function; profiles of these events in this study were similar to those in previous studies of BKM120 monotherapy. No treatment-related deaths occurred. PI3K pathway activation was observed in patients with good clinical response.
Conclusions:
BKM120 monotherapy showed promising efficacy and a manageable toxicity profile even in patients with pretreated advanced ESCC. This study showed the potential target PI3K for ESCC, and further confirmatory trial will be necessary to confirm it. Unique ID issued by UMIN: UMIN 000011217.
Insights
BKM120 demonstrated a 51.2% disease control rate in advanced esophageal squamous cell carcinoma (ESCC). This PI3K inhibitor showed promising efficacy and manageable safety in pretreated patients, warranting further investigation.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- The PI3K/AKT/mTOR pathway is frequently overactive in esophageal squamous cell carcinoma (ESCC).
- BKM120, an oral pan-class I PI3K inhibitor, has shown activity in various cancers.
- Targeting the PI3K pathway presents a promising therapeutic strategy for ESCC.
Purpose of the Study:
- To prospectively evaluate the efficacy, safety, and biomarkers of BKM120 monotherapy in advanced ESCC patients.
- To assess the disease control rate (DCR) as the primary endpoint.
- To explore the correlation between PI3K pathway activation and clinical response.
Main Methods:
- A multicenter phase II study involving BKM120 monotherapy (100 mg/day) in a 28-day cycle.
- Inclusion of pretreated patients with advanced ESCC.
- Comprehensive genomic profiling of tumor samples for gene alteration analysis.
Main Results:
- The study met its primary endpoint with a DCR of 51.2% (95% CI, 35.1-67.1) in the primary analysis population.
- Median progression-free survival was 2.3 months and median overall survival was 9.0 months.
- Common grade 3/4 adverse events included rash, anorexia, hyponatremia, and abnormal hepatic function, consistent with previous studies; no treatment-related deaths occurred.
Conclusions:
- BKM120 monotherapy exhibits promising efficacy and a manageable safety profile in pretreated advanced ESCC.
- The PI3K pathway is a potential therapeutic target for ESCC.
- Further confirmatory trials are necessary to validate these findings.
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