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Ann Oncol. 2014 Aug;25(8):1597-603. doi: 10.1093/annonc/mdu175. Epub 2014 May 14.

Activity and safety of RAD001 (everolimus) in patients affected by biliary tract cancer progressing after prior chemotherapy: a phase II ITMO study.

Author information

1
Day Hospital/Outpatient Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
2
Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan sara.pusceddu@istitutotumori.mi.it.
3
Medical Oncology Unit, Policlinico of Monza, Monza.
4
Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
5
Biostatistician LB Research srl, Cantu.
6
Medical Oncology Unit, Asl 1, Massa Carrara.
7
Medical Oncology Unit, Presidio Ospedaliero Sondrio, Sondrio.
8
Medical Oncology Unit, A.U.O. Maggiore della Carità, Novara.
9
Medical Oncology Unit, Usl 4, Presidio Ospedaliero, Prato.
10
Medical Oncology Unit, Italian Trials in Medical Oncology (ITMO) Group, Fondazione IRCCS Istituto Nazionale Tumori, Milan.
11
Gastro-Intestinal Surgery, Liver Transplantation and Hepatology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

Abstract

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.

KEYWORDS:

advanced biliary tract cancer; everolimus; mTOR

PMID:
24827133
DOI:
10.1093/annonc/mdu175
[Indexed for MEDLINE]

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