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
5472 - Early response evaluation and CEA response in patients treated in a Danish randomized study comparing trifluridine/tipiracil (TAS-102) with or without bevazicumab in patients with chemorefractory metastatic colorectal cancer (mCRC)
Presenter: Camilla Qvortrup
Session: Poster Display session 2
Resources:
Abstract
2037 - Updated survival analysis of the randomized phase III trial comparing S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer (SALTO) by the Dutch Colorectal Cancer Group.
Presenter: Johannes Kwakman
Session: Poster Display session 2
Resources:
Abstract
3053 - JFMC51-1702-C7: Phase II study investigating efficacy and safety of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) in patients (pts) with metastatic colorectal cancer (mCRC) refractory or intolerant to standard chemotherapies.
Presenter: Keisuke Kazama
Session: Poster Display session 2
Resources:
Abstract
3183 - Bevacizumab plus trifluridine/tipiracil in elderly patients with previously untreated metastatic colorectal cancer (KSCC 1602): A single-arm, Phase 2 study
Presenter: Akitaka Makiyama
Session: Poster Display session 2
Resources:
Abstract
3233 - Biweekly TAS-102 and Bevacizumab as a Third-Line Chemotherapy for metastatic colorectal cancer: A Phase II Multicenter Clinical Trial (TAS-CC4 study)
Presenter: Yoichiro Yoshida
Session: Poster Display session 2
Resources:
Abstract
5907 - Liquid biopsy concordance based on clonality and timing of testing in patients with metastatic colorectal cancer
Presenter: Pashtoon Kasi
Session: Poster Display session 2
Resources:
Abstract
1866 - Plasma clearance of RAS mutation under therapeutic pressure is a rare event in metastatic colorectal cancer
Presenter: Emilie Moati
Session: Poster Display session 2
Resources:
Abstract
2312 - High Circulating miR-1247 is a marker for poor prognosis in patients with metastatic colorectal cancer treated with chemotherapy and cetuximab
Presenter: Jakob Schou
Session: Poster Display session 2
Resources:
Abstract
5602 - Clinical relevance of circulating tumor (ct)DNA genotyping for first line cetuximab-based treatment monitoring in metastatic colorectal cancer (mCRC): a prospective multicentric study
Presenter: JOANA Vidal Barrull
Session: Poster Display session 2
Resources:
Abstract
3182 - Clonal hematopoiesis mutations in plasma cfDNA RAS/BRAF genotyping of metastatic colorectal cancer
Presenter: Beili Wang
Session: Poster Display session 2
Resources:
Abstract