Abstract 5336
Background
Epigenetic therapies (epidrugs) modify cancer cells transcriptional programmes and influence all hallmarks of cancer. Thus, epidrugs have been reported to modulate sensitivity to conventional chemotherapy (CCT) preclinically. We explored whether sensitivity to CCT differed before and after epidrug therapy.
Methods
Patients (pts) enrolled in phase 1 trials evaluating epidrugs at the Drug Development Department (DITEP) in Gustave Roussy between March 2010 and May 2017 who received at least one CCT just before and after epidrug therapy were eligible. Progression free survival (PFS) of the CCT line before (PFSpre) and after (PFSpost) epidrug were compared using Wilcoxon signed rank in a paired data subset (uncorrected α-risk).
Results
69% of the 93 eligible pts had haematological malignancies. Epidrug treatments consisted of: IDH inhibitors (IDHi) (30%), HDACi (19%), protein degradation modulators (20%), EZH2i (17%), BETi (12%) and LSD1i (2%); 52 (56%) pts derived clinical benefit (CB) from epidrugs (objective response or SD > 2 months). Median PFSpre and PFSpost were 4.2 and 3.8 months (NS), respectively; PFSpost was significantly worse for pts who did not derive CB from epidrugs (1.8 vs 5.6 months, p = 0.01), whereas significance was lost for pts who derived CB (5.1 vs 3.6 months, NS). Analysis stratified on the CCT type evidenced that PFSpost was significantly worse for pts receiving anthracyclines, topoisomerase inhibitors and alkylating agents (excluding platinum salts) (p = 0.004, p = 0.02 and p = 0.01, respectively), whereas no significant difference was observed for platinum, antimetabolites, anti-microtubule agents or antiangiogenic agents.
Conclusions
Epidrug therapy might modify sensitivity to certain CCT; patients who derive clinical benefit from epidrugs tend to have better PFS on CCT after epidrug treatment than patients who do not benefit from epidrugs. Further studies on larger and homogeneous series are warranted.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
P. Romano-Martin: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Jannsen; Research grant / Funding (self): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Roche. C. Baldini: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Janssen Cilag; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Sanofi. S. Champiat: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Janssen Cilag; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Sanofi. A. Varga: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Janssen Cilag; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Sanofi; Honoraria (self): MSD; Honoraria (self): AstraZeneca; Honoraria (self): Roche. A. Gazzah: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Janssen Cilag; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Sanofi. R. Bahleda: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (institution): Janssen Cilag; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Sanofi. P. Vuagnat: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Janssen Cilag; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Sanofi. A. Hollebecque: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Janssen Cilag; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Sanofi. J. Michot: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Janssen Cilag; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Sanofi. V. Ribrag: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Janssen Cilag; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Sanofi. C. Massard: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Janssen Cilag; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Sanofi; Advisory / Consultancy: Amgen; Advisory / Consultancy: Astellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: BeiGene; Advisory / Consultancy: Lilly; Advisory / Consultancy: MedImmune; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Jannsen. S. Postel Vinay: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Janssen Cilag; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Sanofi; Advisory / Consultancy: Merck; Travel / Accommodation / Expenses: AstraZeneca; Research grant / Funding (self): Roche; Research grant / Funding (self): Boehringer Ingelheim. All other authors have declared no conflicts of interest.
Resources from the same session
1757 - Development of chimeric antigenic receptor (CAR) against VEGFR2 for solid tumor treatment
Presenter: Li-Shuang Ai
Session: Poster Display session 1
Resources:
Abstract
4156 - Triple blockade of EGFR, MEK and PD-L1 as effective antitumor treatment in PD-L1 overexpressing, MEK inhibitor resistant colon cancer cells.
Presenter: Nunzia Matrone
Session: Poster Display session 1
Resources:
Abstract
2949 - EGFR-mediated PD-L1 upregulation in HER2+ breast cancer (BC) cell line models
Presenter: Nicola Gaynor
Session: Poster Display session 1
Resources:
Abstract
4270 - The impact of cortisol on immune cells and its effect on cancer-immune cells co-culture in a 3D spheroid of ovarian cancer
Presenter: Maysa Al-natsheh
Session: Poster Display session 1
Resources:
Abstract
1568 - Application of sonoporation to increase anticancer drug efficacy in 2D and 3D NSCLC cell cultures
Presenter: Vilma Petrikaite
Session: Poster Display session 1
Resources:
Abstract
5400 - Tr1-like cells in human peripheral blood are part of the T effector memory pool and are preferentially stimulated via CD55
Presenter: Iniobong Charles
Session: Poster Display session 1
Resources:
Abstract
5817 - Functional analysis of tumor infiltrating lymphocytes in triple negative breast cancer focusing on granzyme B
Presenter: Hitomi Kawaji
Session: Poster Display session 1
Resources:
Abstract
2287 - Aberrant glycolysis associates with inflammatory tumor microenvironment and promotes metastasis in triple-negative breast cancer
Presenter: Chengwei Lin
Session: Poster Display session 1
Resources:
Abstract
735 - Anti-cancer effects of differentiation-inducing factor-1 in triple negative breast cancer.
Presenter: Fumi Tetsuo
Session: Poster Display session 1
Resources:
Abstract
2105 - The Inhibitory Effect in Oral Squamous Cell Carcinoma Cells by Knocking down Matrix Metalloproteinase 9
Presenter: Xinyan Zhang
Session: Poster Display session 1
Resources:
Abstract