Abstract | BACKGROUND: Extensive extracellular matrix (ECM) remodeling is a hallmark of metastatic pancreatic ductal adenocarcinoma ( mPDA). We investigated fragments of collagen types III (C3M, PRO-C3), VI (PRO-C6), and VIII (C8-C), and versican (VCANM) in plasma as biomarkers for predicting progression-free survival (PFS) and overall survival (OS) in patients with mPDA treated with pegvorhyaluronidase alfa, a biologic that degrades the ECM component hyaluronan (HA), in a randomized phase 2 study (HALO109-202). METHODS: RESULTS: PFS was improved with PAG vs. AG in Stage 1 patients with high C3M/ PRO-C3 ratio (median cut-off): median PFS (mPFS) 8.0 vs. 5.3 months, P = 0.031; HR = 0.40; 95% CI 0.17-0.92). High C3M/ PRO-C3 ratio was validated in Stage 2 patients by predicting a PFS benefit of PAG vs. AG (mPFS: 8.8 vs. 3.4 months, P = 0.046; HR = 0.46; 95% CI 0.21-0.98). OS was also improved in patients with high C3M/ PRO-C3 ratio treated with PAG vs. AG (mOS 13.8 vs 8.5 months, P = 0.009; HR = 0.35; 95% CI 0.16-0.77). Interestingly, high C3M/ PRO-C3 ratio predicted for a PFS benefit to PAG vs. AG both in patients with HA-low tumors (HR = 0.36; 95% CI 0.17-0.79) and HA-high tumors (HR = 0.20; 95% CI 0.06-0.69). CONCLUSIONS: The C3M/ PRO-C3 ratio measuring type III collagen turnover in plasma has potential as a blood-based predictive biomarker in patients with mPDA and provides additional value to a HA biopsy when applied for patient selection. TRIAL REGISTRATION: NCT01839487. Registered 25 April 2016.
|
Authors | Song Wang, Cecilie L Bager, Morten A Karsdal, Dimitrios Chondros, Darin Taverna, Nicholas Willumsen |
Journal | Journal of translational medicine
(J Transl Med)
Vol. 19
Issue 1
Pg. 39
(01 21 2021)
ISSN: 1479-5876 [Electronic] England |
PMID | 33478521
(Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Albumins
- Biomarkers
- Hyaluronoglucosaminidase
- PEGPH20
- Paclitaxel
|
Topics |
- Adenocarcinoma
- Albumins
(therapeutic use)
- Antineoplastic Combined Chemotherapy Protocols
- Biomarkers
- Extracellular Matrix
- Humans
- Hyaluronoglucosaminidase
- Paclitaxel
(therapeutic use)
- Pancreatic Neoplasms
(drug therapy)
|