Introduction
Metastatic pancreatic adenocarcinoma (mPDAC) has poor prognosis with a 5-year survival rate of 3%. In non-metastatic, unresectable locally advanced pancreatic cancer (LAPC) patients, endoscopic-ultrasound (EUS)-guided intra-tumoral 32P-microparticles implantation resulted in 90.5% local disease control rate [LDCR], defined as Stable Disease [SD] or better, at 16 weeks1. This is the first study to examine the outcome of 32P-microparticles (OncoSil™; OncoSil Medical) implantation, in combination with chemotherapy, for treatment of patients with mPDAC.
Aims & Methods
Outcome data of mPDAC patients treated with combination of chemotherapy and intra-tumoral 32P microparticles (8% of tumour volume, delivering ~100Gy to the tumour) from 5 centres in Australia and UK were retrospectively reviewed. In all cases, 32P implantation was performed after at least 2 cycles of chemotherapy, which were either FOLFIRINOX or gemcitabine/nab-paclitaxel (Gen-Nab). Data were expressed as median value and P<0.05 was considered as significant.
Results
14 patients (7F:7M; age: 64.5 years; ECOG 0/1/2: 21.4%/57.1%/21.4%) were treated with Gem-Nab (n=10) and FOLFIRINOX (n=4) prior to 32P-microparticles implantation. Patients had a median of 3 metastases (range, 1-7) in liver (42.9%), lung (35.7%), liver/lung (7.1%), liver/peritoneum (7.1%) or lung/peritoneum (7.1%), with median primary tumour longest diameter [LD] and volume of 40.5mm and 21.8cm3, respectively. 32P microparticles were implanted with a 100% technical success, at a median 3.1 months from the initial chemotherapy. Prior to OncoSilTM implantation, only 50% (n=7) had evidence of either stable disease (n=5) or partial response (n=2) based on RECIST criteria. After OncoSilTM implantation, local disease control rate was 100% at 3 months (stable disease:10 patients; partial response: 4 patients). There was a median 25% reduction in primary tumour LD, with 1 (7%) patient having a marked response and underwent resection (R0 on histology). Median CA19-9 declined from 856.5U/mL to 72U/mL. After a median follow-up of 35.3 months, site of progression after Oncosil implantation were: distant (n=8), local/distant (n=4), local (n=1) and no progression (n=1). Median progression-free survival (PFS) after 32P implantation was 5.6 months (95% CI: 4.3-non-calculable [nc]), and the overall median survival was 13.9 months (95% CI: 12.2-nc). No Grade 4/5 acute toxicities were observed; 3 (21.4%) patients had device- or procedure-related Grade 1/2 AEs (abdominal pain; nausea; fatigue; dyspepsia) that were also attributed to chemotherapy.
Conclusion
The addition of EUS-guided 32P-microparticles implantation to standard chemotherapy is feasible and safe for mPDAC patients, with 100% local disease control rate at 3 months post-implantation. This promising data suggests the role of combined intra-tumoral 32P-microparticles and chemotherapy in the treatment of mPDAC and warrants further evaluation in a large prospective trial.
References
1. Ross, P.J., et al., PanCO: An open-label, single-arm pilot study of phosphorus-32 (P-32; Oncosil) microparticles in patients with unresectable locally advanced pancreatic adenocarcinoma (LAPC) in combination with FOLFIRINOX or gemcitabine + nab-paclitaxel (GNP) chemotherapies. Journal of Clinical Oncology, 2019. 37(15_suppl): p. 4125-4125.
Disclosure
Authors include 2 members of OncoSil Medical whom have assisted in obtaining data from multiple centres however first author collated and analysed data.