Abstract 3303
Background
In pancreatic cancer desmoplasia is a central feature of the tumour microenvironment. Growing evidence suggests that by targeting both tumour cells and tumour stoma, treatment efficacy is increased. LDE225 is a pharmacological Hedgehog signaling pathway inhibitor and is thought to specifically target tumour stroma. We investigated the combined use of LDE225 and chemotherapy in pancreatic cancer.
Methods
This was a multi-center, dose finding, phase I/II study for patients with metastatic pancreatic cancer. In part I of the study, we established the maximum tolerated dose of LDE225 to be 200 mg once daily co-administered with gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 on days 1, 8 and 15 of a 4 week cycle (ESMO 2017). The objective of the phase II part was to evaluate efficacy and safety of the treatment combination and assess tumour cellularity and vascularity with diffusion weighted magnetic resonance imaging and dynamic contrast enhanced magnetic resonance imaging. Tumour response evaluation was performed using CT scan. Here we report on the phase II part of the study.
Results
In the phase II part we included 25 patients. Most patients had WHO performance status of 0-1 (92%) and 60% were male. All patients received prior chemotherapy. Patients were treated with a median number of two cycles (IQR 1.5-5.0). Four therapy related grade 4 adverse events (AE) were observed: sepsis (2), neutropenia (2), and one grade 5 (sepsis). Most common grade 3 therapy related AEs were neutropenia (37%) and diarrhea (14.8%). Patients discontinued treatment because of progressive disease (20), bacterial infection (1), sepsis (1) and diminished quality of life (1). 2 patients are still alive. In 19 patients target lesion response was evaluable, 2 patients had partial response (10%), stable disease was seen in 10 patients (53%) and 7 patients had progressive disease (37%). The median overall survival was 6 months (IQR 3.0-8.5). Tumour vascularity and cellularity is currently being analyzed in 25 patients.
Conclusions
This study shows that LDE225 in combination with gemcitabine and nab-paclitaxel is well-tolerated in patients with metastatic pancreatic cancer and has promising efficacy.
Clinical trial identification
NCT02358161.
Editorial acknowledgement
Legal entity responsible for the study
J.W. Wilmink.
Funding
Novartis, Celgene and Sunpharma.
Disclosure
H.W.M. van Laarhoven: Research grant / Funding (institution): Roche; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Lily; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Serono; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Nordic; Research grant / Funding (institution): Philips. H.W. Wilmink: Research grant / Funding (institution): Servier; Research grant / Funding (institution): Halozyme; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Advisory / Consultancy: Shire. All other authors have declared no conflicts of interest.
Resources from the same session
5205 - Immune status of patients with different stages of colorectal cancer with and without circulating tumor cells
Presenter: Anastasia Sitkovskaya
Session: Poster Display session 2
Resources:
Abstract
5658 - Detection of 5-hydroxymethylcytosine in Circulating-Free DNA for Early Diagnosis of Colorectal Cancer
Presenter: Tianyu Liu
Session: Poster Display session 2
Resources:
Abstract
5779 - Detection of 5-hydroxymethylcytosine in Circulating-Free DNA for Prediction of The Efficacy of Conversion Therapy for Colorectal Cancer Liver Metastases
Presenter: Wenju Chang
Session: Poster Display session 2
Resources:
Abstract
4672 - mCRC gene profiling using the Idylla platform
Presenter: Christopher Bricogne
Session: Poster Display session 2
Resources:
Abstract
3393 - PIK3CA mutation in metastatic colorectal cancer (mCRC): association with clinico-pathological features and outcome
Presenter: Valentina Fanotto
Session: Poster Display session 2
Resources:
Abstract
1317 - Patient-Derived Xenografts (PDX) Identifies JMJD6 Inhibitor as an Effective Therapeutic Medicine in Colorectal Cancer.
Presenter: Feng Ye
Session: Poster Display session 2
Resources:
Abstract
1228 - DACH1 induced stemness of intestinal organoids by directly suppressing BMP signaling and contributes to intestinal tumorigenesis
Presenter: Xiang Hu
Session: Poster Display session 2
Resources:
Abstract
1147 - miR-148a inhibits early relapsed colorectal cancers and the secretion of VEGF by indirectly targeting HIF-1α under non-hypoxia/hypoxia conditions
Presenter: Hsiang-lin Tsai
Session: Poster Display session 2
Resources:
Abstract
1158 - Long noncoding RNA CASC21 promotes cell proliferation and metastasis in colon cancer.
Presenter: Qun Zhang
Session: Poster Display session 2
Resources:
Abstract
1259 - Prognostic and Predictive Impact On FMS-like Tyrosine Kinase 3 (FLT3) Amplification In Patients With Metastatic Colorectal Cancer
Presenter: Hiroko Hasegawa
Session: Poster Display session 2
Resources:
Abstract