Abstract 2773
Background
Etoposide toniribate (also known as EDO-S7.1, and previously known as CAP7.1), a novel topoisomerase II inhibitor, is activated in the presence of carboxylesterases. In specific tumor cell lines, it was found to be more active than etoposide, with in vivo activity demonstrated in several drug-resistant tumor models. Anti-tumor activity was confirmed in a Phase II randomized study in patients (pts) with relapsed BTC.
Methods
Pts with BTC and disease progression after ≥1 line of chemotherapy were randomized 1:1 to 3-week cycles of etoposide toniribate (200 or 150mg/m2; iv on days 1–5), or best supportive care (BSC). Pts who progressed on BSC crossed over to receive etoposide toniribate. Efficacy data collected after crossover were evaluated separately as part of this post-hoc exploratory analysis.
Results
The per protocol analysis set included 19 pts: 10 pts were randomized to BSC, and crossed over to etoposide toniribate after disease progression, 9 pts were randomized directly to the etoposide toniribate treatment arm. Treatment after crossover from BSC to etoposide toniribate was associated with a trend for improved disease control: n/N (%; 95% CI) 4/10 (40%; 12.2, 73.8) vs 2/10 (20%; 2.5, 55.6), with tumor control achieved in 4/10 patients (1 pt partial response, 3 pts stable disease). Risk of disease progression was 2.33 times higher during BSC treatment vs after crossover to etoposide toniribate. Crossover from BSC to etoposide toniribate was associated with a trend for prolonged median PFS (39 vs 50 days). Median OS for pooled etoposide toniribate and crossover pts was 145 (59, 243) days, estimated 1-year OS 14.1%. Median (95% CI) OS for etoposide toniribate vs crossover pts was 180 (43, 468) vs 83 (11, 243) days, HR 0.39 (0.13, 1.18), estimated 1-year OS 29.6% (5.2%, 60.7%) vs 0%.
Conclusions
This post-hoc analysis provides further evidence for the efficacy of etoposide toniribate and suggests that early initiation in pts with advanced BTC may offer a potential survival benefit. The efficacy of etoposide toniribate will be further investigated in a planned phase III study. Funding: CellAct Pharm GmbH and Mundipharma EDO GmbH.
Clinical trial identification
NCT02094560.
Editorial acknowledgement
Sarah Birch, PhD, at Makara Health Communications Ltd, UK, funded by Mundibiopharma Ltd.
Legal entity responsible for the study
CellAct Pharma GmbH.
Funding
CellAct Pharma GmbH, Mundipharma EDO GmbH.
Disclosure
U. Pape: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Shire; Honoraria (self), Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Ipsen. S. Kasper: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy: Servier; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: MSD; Research grant / Funding (self): Celgene; Research grant / Funding (self), Travel / Accommodation / Expenses: Lilly. J. Meiler: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Sanofi/Aventis. M. Sinn: Honoraria (self): Amgen; Honoraria (self), Research grant / Funding (self): Leo Pharma; Honoraria (self), Advisory / Consultancy: Sanofi; Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Boston Biomedical; Research grant / Funding (self): Incyte; Research grant / Funding (self): Merck Sharp and Dohme; Research grant / Funding (self): Servier; Research grant / Funding (self): Taiho Pharmaceutical. H. Jansen: Advisory / Consultancy: CellAct Pharma. T. Mehrling: Leadership role, Full / Part-time employment: Mundipharma EDO. K. Hilgier: Advisory / Consultancy: Mundipharma EDO. I. Wagner: Full / Part-time employment: Mundipharma EDO. N. Utku: Honoraria (self), Advisory / Consultancy, Leadership role, Research grant / Funding (self), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: CellAct Pharma; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Mundipharma EDO; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Ingelheim. All other authors have declared no conflicts of interest.
Resources from the same session
5694 - Findings from a new specialist remote Counselling Service for Neuroendocrine Neoplasm (NEN) patients and family members
Presenter: Catherine Bouvier
Session: Poster Display session 2
Resources:
Abstract
4725 - Hematologic malignancies in temozolomide-treated metastatic pancreatic neuroendocrine tumors
Presenter: Nicole Balmaceda
Session: Poster Display session 2
Resources:
Abstract
5842 - Efficacy and toxicity of combination chemotherapy with cyclophosphamide, vincristine and an anthracycline in patients with metastatic extrapulmonary neuroendocrine carcinoma
Presenter: Leonidas Apostolidis
Session: Poster Display session 2
Resources:
Abstract
1543 - An Australian multi-centre experience of the use of peptide receptor radionuclide therapy for bronchial carcinoid tumours.
Presenter: Lisi Lim
Session: Poster Display session 2
Resources:
Abstract
4175 - Extra-pulmonary (EP) high grade (HG) neuroendocrine carcinoma (NEC): real-life outcomes of fifty-eight patients from a Portuguese cancer center.
Presenter: Rita Conde
Session: Poster Display session 2
Resources:
Abstract
3274 - Efficacy of immune check-point inhibitors (ICPi) in large cell neuroendocrine tumors of lung (LCNET)
Presenter: Shira Sherman
Session: Poster Display session 2
Resources:
Abstract
3534 - HORMONET: Study of Tamoxifen in Well Differentiated Neuroendocrine Tumors and Hormone Receptor Positive Expression
Presenter: Milton Barros
Session: Poster Display session 2
Resources:
Abstract
2137 - Clinical utility of Metabolic Tumor Volume in Papillary Thyroid Carcinoma
Presenter: Norihiko Takemoto
Session: Poster Display session 2
Resources:
Abstract
3864 - Correlation of thyroglobulin (Tg) oscillations with progression-free survival (PFS) in patients with radioactive iodine-refractory (RAI-R) differentiated thyroid carcinoma (DTC) treated with multikinase inhibitors (MKI).
Presenter: Jorge Hernando Cubero
Session: Poster Display session 2
Resources:
Abstract
2820 - Analytical validation of a thyroid cancer diagnostic method based on the relative quantification of CLDN10, HMGA2 and LAMB3 expression
Presenter: Mateus Barrosfilho
Session: Poster Display session 2
Resources:
Abstract