Outcomes of phosphorus-32 microparticle intratumoural implantation added to chemotherapy in patients with metastatic pancreatic adenocarcinoma

Metastatic pancreatic adenocarcinoma (mPDAC) has a 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 phosphorus-32 ( 32 P)-microparticles implantation resulted in local disease control rate [LDCR] (defined as Stable Disease [SD] or better) at 16 weeks (3 months post-implantation) of 90.5%. This is the first multicentre analysis of 32 P-microparticles implantation in patients with mPDAC.

Patients with mPDAC treated with chemotherapy and intratumoural 32 P-microparticles (OncoSil™; OncoSil Medical) delivering 100Gy target tumour absorbed dose from 5 centres in Australia and UK were retrospectively analysed. Patients received 32 P-microparticles in the PanCO study (metastases identified post-enrolment by PET-imaging) or special access scheme.

14 patients were treated (male: 50%; median age: 64.5 years; ECOG 0/1/2: 21.4%/57.1%/21.4%). Median primary tumour longest diameter [LD] and volume were 40.5mm and 21.8cm 3, respectively. 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%). Patients received chemotherapy (FOLFIRINOX [n=4; 1 2 nd -line] or gemcitabine/nab-paclitaxel [n=10; 2 2 nd -line]). 32 P-microparticles were implanted at median 3.1 months from initial chemotherapy commencing [baseline], 7 patients at median 1.1 months (range, 0.7-2.5 [early cohort]) and 7 at median 4.9 months (range, 3.6-7.9 [delayed cohort]). Pre-implantation, RECIST response was 2 (14.3%) Partial Response [PR], 5 (35.7%) SD, 1 (7.1%) local Progressive Disease [PD] and 2 (14.3%) distant PD; 4 (28.6%) had no intermediate scan. LDCR at 3 months post-implantation was 100%. Best RECIST primary tumour response vs . pre-implantation scan was 4 (28.6%) PR, including the patient with local PD pre-implantation, plus 10 (71.4%) SD. The early implantation cohort had a mean –22.0% (median –25.0%) maximal decrease in primary tumour LD vs . baseline. The delayed implantation cohort had a mean –30.2% (median –25.0%) maximal decrease in primary tumour LD vs . pre-implantation, compared to a mean –8.6% (median –4.2%) pre-implantation decrease vs . baseline. One patient (7.1%) had a good response and thus underwent surgical resection (R0 on histology). Median CA19-9 in patients with baseline >35U/mL decreased from 856.5U/mL to 72U/mL at nadir; 6/10 patients had >50% decrease. Site(s) of first progression post-implantation were: 57.1% distant, 28.6% local/distant, 7.1% local and 7.1% no progression; 2 patients (14.3%) with distant PD developed local PD (5 and 30 months later). Median follow-up was 35.3 months. Although median progression-free survival (PFS) from 32 P-implantation was 5.6 months (95% CI: 4.3-non-calculable [nc]), local PFS was longer than distant PFS (9.4 (95% CI: 5.9-nc) vs . 5.6 (95% CI: 4.3-nc)). From chemotherapy commencement, median overall survival was 13.9 (95% CI: 12.2-nc) months. 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.

EUS-guided 32 P-microparticles implantation to deliver 100Gy to target tumour appears safe in mPDAC patients receiving chemotherapy, with encouraging outcomes including 100% LDCR at 3 months post-implantation. This retrospective analysis highlights the potential clinical benefits, particularly of local tumour control and overall survival, in a metastatic cohort in whom outcomes are often poor.

The authors.

Has not received any funding.

H. Wasan: Honoraria (self): Servier, Incyte, Pierre Farbre; Advisory / Consultancy: Servier, Incyte, Pierre Farbre; Speaker Bureau / Expert testimony: Servier, Incyte, Pierre Farbre; Research grant / Funding (institution): Pfizer, Sirtex; Travel / Accommodation / Expenses: Servier, Incyte, Pierre Farbre. D. Turner: Shareholder / Stockholder / Stock options: OncoSil Medical Limited; Full / Part-time employment: OncoSil Medical Limited. All other authors have declared no conflicts of interest.