Abstract 2603
Background
REG is a small-molecule multikinase inhibitor involved in normal cellular functions and pathologic processes such as oncogenesis, angiogenesis, and tumor immunity. REG is approved for the treatment of advanced colorectal cancer, gastrointestinal stromal tumors, and hepatocellular carcinoma. REG alone is currently being evaluated for its tolerability and safety in pediatric cancers in a clinical phase 1 study. Preclinically, we investigated a series of drugs, which are established or emerging for the treatment of pediatric patients with RMS, for their combination potential with REG to support its clinical development in pediatric indications.
Methods
Proliferation assays were performed in vitro. In vivo, subcutaneous xenografts derived from pediatric alveolar (RH30) and embryonal (RD) RMS tumor cell lines were treated with REG alone and in combination with 13 different compounds including a combination with irinotecan (IRI) and vincristine (VINC). A study design with one mouse per group and a stepwise dose escalation was applied. The body weight of the mice was closely monitored for tolerability and the tumor growth was determined by caliper measurements. Treatment was for four weeks and the time to tumor regression was followed thereafter.
Results
The pattern of response was heterogeneous, ranging from complete regression (CR) to insensitivity. REG alone at an oral dose of 10mg/kg/d delayed the growth of both RMS xenografts. CRs were observed for IRI (both models), paclitaxel (RH30 model), and VINC (RD model) alone near their maximum tolerated doses in mice. The strong monotherapy effects of IRI and VINC preclude a clear demonstration of a combination benefit with REG in this study. Beneficial combination effects were observed for some other drugs. IRI appeared as the most favorable combination partner of REG of the tested drugs. Surprisingly, the RH30 model was insensitive to VINC in this study. Treatment interruptions were required in some cases of treatment intolerability, but no drug-related deaths were observed.
Conclusions
These results warrant further exploration of a combination of REG with IRI and VINC in pediatric RMS.
Clinical trial identification
Legal entity responsible for the study
Bayer.
Funding
Bayer.
Editorial Acknowledgement
Disclosure
D. Zopf, Y. Tsvetkova: Full-time employment: Bayer AG. J. Hoffmann: CEO and shareholder: EPO GmbH.
Resources from the same session
2595 - Real-Life Utilization of Genomic testing for invasive Breast Cancer patients in Italy and France reduces Chemotherapy Recommendations
Presenter: Sandro Barni
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
2343 - Benefit of adjuvant chemotherapy in hormone receptor-positive, HER2-negative, invasive lobular carcinoma of the breast
Presenter: Alexandre De Nonneville
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
2990 - Baseline lymphocyte counts predict distant recurrence in early breast cancer
Presenter: Gun Min Kim
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
4532 - A propensity score analysis exploring the impact of the addition of adjuvant chemotherapy (aCT) to hormone therapy (aHT) in a multi-center series of resected luminal early stage pure Invasive Lobular Breast Carcinoma (ILC).
Presenter: Luisa Carbognin
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
2344 - Benefit of Adjuvant Systemic Therapies in HR+ HER2- pT1ab Node-Negative Breast Carcinomas
Presenter: Alexandre De Nonneville
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
3525 - Anti-proliferative effect of oral metronomic vinorelbine in PAM50 Luminal/HER2-negative early breast cancer (SOLTI-1501 VENTANA): an open-label, randomized, three-arm, multicenter, window-of-opportunity study
Presenter: Aleix Prat
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
3908 - Clinicopathologic significance of androgen receptor expression and discordant receptor status during progression in breast cancer
Presenter: Chan Heun Park
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
4075 - The outcomes of early breast cancers utilizing the Oncotype Dx Recurrence score (RS) instead of Clinico-pathological (CP) factors for prognostic risk assessment: A Single Institution Experience
Presenter: Adhar Alsayed
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
738 - Circulating tumor cells as a prognostic marker in non metastatic breast cancer patients.
Presenter: Summar Elmorshidy
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
3151 - Molecular subtyping of breast cancer by dedicated breast PET
Presenter: Satoshi Sueoka
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract