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
1619 - Meta-analysis of KRAS Mutation as prognostic factor in patients (pts.) with resection of colorectal (CRC) liver metastases: Tumor burden and Sideness analysis.
Presenter: Maria Romina Luca
Session: Poster Display session 2
Resources:
Abstract
2104 - Clinical implications of regorafenib-induced hypothyroidism in metastatic colorectal cancer refractory to standard therapies: A prospective evaluation
Presenter: Jwa Hoon Kim
Session: Poster Display session 2
Resources:
Abstract
2143 - Clinical impact of BRAF V600E mutations in patients (pts) with resectable solitary colorectal liver metastases (CRLM)
Presenter: Shin Kobayashi
Session: Poster Display session 2
Resources:
Abstract
3136 - Trifluridine/tipiracil in metastatic colorectal cancer: an updated multicentre real-world analysis on efficacy, safety and predictive factors.
Presenter: Chara Stavraka
Session: Poster Display session 2
Resources:
Abstract
4234 - Correlation between p53 expression and clinical outcome in RAS/BRAF wild type metastatic colorectal cancer patients receiving later-line irinotecan-cetuximab
Presenter: Eleonora Lai
Session: Poster Display session 2
Resources:
Abstract
4287 - Safety and effectiveness of aflibercept + FOLFIRI for the treatment of patients with metastatic colorectal cancer (mCRC): OZONE secondary analyses
Presenter: Ian Chau
Session: Poster Display session 2
Resources:
Abstract
1820 - A Phase Ib study of the safety and efficacy of atezolizumab (atezo) + bevacizumab (bev) + cobimetinib (cobi) in patients (pts) with metastatic colorectal cancer (mCRC)
Presenter: Johanna Bendell
Session: Poster Display session 2
Resources:
Abstract
5644 - Development and validation of a metastasis-associated immune prognostic model for concurrent metastatic colorectal cancer
Presenter: Zhiwen Luo
Session: Poster Display session 2
Resources:
Abstract
5697 - Prognostic role of blood cell count-based immuno-inflammatory parameters in the Valentino trial
Presenter: Giovanni Fuca
Session: Poster Display session 2
Resources:
Abstract
4704 - Evaluation of safety, immunogenicity and preliminary efficacy of PolyPEPI1018 vaccine in subjects with metastatic colorectal cancer (mCRC) with a predictive biomarker
Presenter: Joleen Hubbard
Session: Poster Display session 2
Resources:
Abstract