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Comparison of resected vs non-resected patients with unresectable locally advanced pancreatic cancer (LAPC) receiving P-32 microparticles with gemcitabine/nab-paclitaxel or FOLFIRINOX chemotherapy in the PanCO study
Background
Unresectable LAPC has a poor prognosis. Current standard-of-care (SoC) is limited to chemotherapy or chemo-radiotherapy. Brachytherapy using a device containing beta-radiation-emitting Phosphorous-32 (P-32) microparticles is implanted directly into pancreatic tumours via endoscopic-ultrasound (EUS) guidance. We report a post-hoc analysis of resected vs. non-resected cohorts in PanCO, a single-arm, multi-centre, pilot study of P-32 microparticles with SoC chemotherapy in patients with unresectable LAPC.
Methods
Eligible patients with unresectable LAPC and ECOG 0/1 received either gemcitabine/nab-paclitaxel or FOLFIRINOX chemotherapy. P-32 microparticles (OncoSil™; OncoSil Medical) implantation was planned at weeks 4-5. P-32 activity was calculated from participants’ tumour volume to deliver 100Gy absorbed dose. The primary endpoint was safety/tolerability graded using CTCAE v4.0. Response was assessed by independent central reader using RECIST 1.1 with 8-weekly CT scans and FDG-PET scans at baseline and week 12.
Results
Fifty patients were enrolled (Intention-to-Treat); 42 participants were implanted with P-32 microparticles (Per Protocol [PP] population) at a median of 31 days. 40 participants received gemcitabine/nab-paclitaxel and 10 FOLFIRINOX (PP: 34/8, respectively). Median follow-up was 31.6 months. Ten participants (23.8% PP; 9 received gemcitabine/nab-paclitaxel, 1 FOLFIRINOX) underwent pancreaticoduodenectomy following repeat staging at a median of 5.8 months post-enrolment (4.4 months post-implant); 8 (80%) achieved R0 margins. Four further participants were sufficiently down-staged to be technically considered for surgical resection, but could not undergo surgery due to metastases, co-morbidities or patient choice. Baseline characteristics for resected and non-resected participants were similar for age (median 65 vs. 68 years), longest tumour diameter (median 4.5 vs. 4.5cm) and tumour volume (median 23.2 vs. 24.4cc), respectively. More resected participants were ECOG 0 (80% vs. 45%) and female (60.0% vs. 28.1%), respectively. Median relative dose intensity in resected vs. non-resected participants was 70.6% vs. 54.2% for 4 cycles gemcitabine/nab-paclitaxel and 82.9% vs. 71.2% for 6 cycles FOLFIRINOX. Resected participants compared with non-resected patients had greater response by median decrease from baseline at week 16 in tumour longest diameter (-21.5% vs.-8.1%), tumour volume (-59.5% vs. -30.8%), CA 19-9 (-95.9% vs. -75.2% in those with baseline >35 U/mL) and FDG-PET at week 12 (TLG: -95.0% vs. -75.2%; SUVMax: -80.2% vs. -39.8%). Treatment-emergent AEs (TEAEs) attributed to P-32 microparticles or implantation procedure were infrequent (41 vs. 609 attributed to chemotherapy; PP population). Only 39 TEAEs were reported £30 days post-resection, in line with surgical experience, with none attributed to the device or implantation. 180-day post-resection mortality was 0%. Median survival in the resected cohort was not reached (95% CI: 21.1-non-calculable; median follow-up: 32.0 months). Four resected participants survived for 18.8-22.1 months post-enrolment; 6 remained alive at study completion (5 without recurrence) 26.4-35.3 months post-enrolment.
Conclusions
EUS-guided P-32 microparticle implantation appears safe, with encouraging clinical outcomes and may convert unresectable LAPC to surgical resection. Nearly one-in-four PP participants (23.8%) underwent surgical resection with curative intent and one-in-three (33.3%) were technically resectable. Resected participants had a substantial response to treatment compared to non-resected participants, particularly with respect to decrease in tumour volume, and encouraging survival. Further clinical studies adding P-32 microparticles to SoC chemotherapy are planned.
Legal entity responsible for the study
OncoSil Medical Ltd. Sydney, Australia.
Funding
OncoSil Medical Ltd., Sydney, Australia.
Disclosures
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.
