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Updated: Apr 29, 2026
Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma
Published on: May 24, 2024
Activity and safety of RAD001 (everolimus) in patients affected by biliary tract cancer progressing after prior
R Buzzoni1, S Pusceddu2, E Bajetta3
1Day Hospital/Outpatient Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
Background:
Biliary tract cancer (BTC) is a highly lethal disease for which the best available therapy remains undetermined. The mammalian target of rapamycin (mTOR) pathway is up-regulated in several cancers, including BTC, and preclinical evidence indicates that mTOR inhibition may be effective in the treatment of BTC. We sought to evaluate the activity and tolerability of the mTOR inhibitor RAD001-everolimus-in patients with BTC progressing after prior chemotherapy.
Patients And Methods:
This was an open-label, single-arm, phase II study (EUDRACT 2008-007152-94) conducted in eight sites in Italy. Patients with locally advanced, metastatic or recurrent BTC progressing despite previous chemotherapy received a daily oral dose of everolimus 10 mg administered continuously in 28-day cycles. The two primary end points were disease control rate (DCR) and objective response rate (ORR). Secondary end points were progression-free survival (PFS), overall survival (OS) and time-to-progression (TTP).
Results:
Thirty-nine patients were enrolled. The DCR was 44.7%, and the ORR was 5.1%. One patient showed a partial response at 2 months and one patient showed a complete response sustained up to 8 months. The median (95% confidence interval) PFS was 3.2 (1.8-4.0) months, and the median OS was 7.7 (5.5-13.2) months. The median TTP was 2.0 (1.7-3.7) months. Most common toxicities were asthenia (43.6%), thrombocytopenia (35.9%), pyrexia (30.8%) and erythema, mainly of mild-to-moderate severity. Two patients required dose reduction due to adverse events.
Conclusion:
Everolimus demonstrated a favourable toxicity profile and encouraging anti-tumour activity. Further trials are needed to establish the role of everolimus in the treatment of BTC. EUDRACT 2008-007152-94.
Insights
Everolimus, an mTOR inhibitor, showed a favorable toxicity profile and anti-tumor activity in patients with biliary tract cancer (BTC) after chemotherapy. Further trials are needed to confirm its role in BTC treatment.
Area of Science:
- Oncology
- Pharmacology
Background:
- Biliary tract cancer (BTC) has limited treatment options, with the mammalian target of rapamycin (mTOR) pathway being a potential therapeutic target.
- Preclinical studies suggest mTOR inhibition may be effective for BTC treatment.
Purpose of the Study:
- To evaluate the efficacy and safety of RAD001 (everolimus), an mTOR inhibitor, in patients with BTC who progressed after prior chemotherapy.
Main Methods:
- An open-label, single-arm, phase II study enrolled 39 patients with advanced or recurrent BTC.
- Patients received oral everolimus 10 mg daily in 28-day cycles.
- Primary endpoints included disease control rate (DCR) and objective response rate (ORR); secondary endpoints included progression-free survival (PFS) and overall survival (OS).
Main Results:
- The DCR was 44.7% and the ORR was 5.1%, with one complete response and one partial response observed.
- Median PFS was 3.2 months, and median OS was 7.7 months.
- Common toxicities included asthenia, thrombocytopenia, and pyrexia, mostly mild-to-moderate.
Conclusions:
- Everolimus demonstrated a favorable toxicity profile and encouraging anti-tumor activity in this patient population.
- Further clinical trials are warranted to establish the role of everolimus in the treatment of BTC.
