P-260 Naïve indirect treatment comparison of PanCO, a pilot study of OncoSil P-32 microparticles combined with gemcitabine + nab-paclitaxel or FOLFIRINOX chemotherapy versus standard-of-care treatment in unresectable locally advanced pancreatic cancer

Abstract

Pancreatic cancer is a malignancy with a very poor prognosis and remains an area of high unmet medical need. Current standard treatment for patients with unresectable locally advanced pancreatic cancer (LAPC) is limited to chemotherapy (CT-only) or chemoradiotherapy following induction CT (ICT+CCRT). International guidelines (e.g. ESMO, ASCO and NCCN) recommend gemcitabine monotherapy as well as other regimens containing gemcitabine or fluoropyrimidines (capecitabine, 5FU) plus other agents, or ICT+CCRT, for the treatment of LAPC. Brachytherapy using beta-emitting phosphorus-32 (P-32) microparticles enables a predetermined radiation dose to be implanted into pancreatic tumours via endoscopic ultrasound (EUS) guidance. The results of a prospective, interventional, open-label, single-arm pilot study of P-32 microparticles (OncoSil TM ; OncoSil Medical) combined with gemcitabine + nab-paclitaxel or FOLFIRINOX chemotherapy demonstrated encouraging safety and efficacy in patients with unresectable LAPC (the PanCO study: NCT03003078). In the absence of a head-to-head randomised controlled trial, a naïve indirect treatment comparison was used to assess the results of the PanCO study against state-of-the-art (SOTA) therapy obtained from a systematic literature review (SLR) of published scientific literature from prospective clinical studies. A SLR was conducted to identify published clinical data on SOTA/‘standard-of-care’ treatments from prospective phase II and III clinical studies in patients with unresectable LAPC treated with CT-only or ICT+CCRT. The SLR outcomes were then compared with the results of the PanCO study in a naïve indirect treatment comparison and analysed using a binomial test. The SLR identified clinical outcomes including overall survival (OS), progression-free survival (PFS), one-year survival, resection rate, disease control rate (DCR) and overall response rate (ORR). In total, there were 46 included studies, comprising 57 arms and 4,327 patients, 2,350 of whom had LAPC. The PanCO study enrolled 50 patients (Intention-to-Treat [ITT] population) of which 42 were implanted with P-32 microparticles (Per Protocol [PP] population), with a median follow-up of 16.1 months. Median OS was significantly longer (p<0.001) in the PanCO study than CT-only and/or ICT+CRT regimens (PanCO PP: 16.0 months; ITT: 15.5 months; vs. SLR combined: 12.7 months; CT-only: 12.7 months; ICT+CCRT: 12.6 months), representing a ∼20% reduction in the risk of death compared to CT-only and ICT+CCRT studies (Hazard Ratio PP: 0.79; ITT: 0.82). One-year survival rates in PanCO were significantly higher than SOTA (p<0.001; PanCO PP: 64.0%; ITT: 63.4%; vs. SLR combined: 52.5%; CT-only: 50.4%; ICT+CCRT: 55.2%). The rate of surgical resection in PanCO was significantly greater than SOTA (p<0.001; PanCO PP: 23.8%; ITT: 20.0%; vs. SLR combined: 9.9%; CT-only: 7.7%; ICT+CCRT: 11.5%). Median PFS was significantly longer (p<0.001) than the SLR combined or CT-only regimens (PanCO PP and ITT: 9.3 months; vs. SLR combined: 7.6 months; CT-only: 6.6 months; ICT+CCRT: 9.1 months). DCR and ORR were also significantly higher than the combined SLR or CT-only regimens (ORR/DCR: PanCO PP 31.0%/100%; ITT: 29.8%/95.7%; vs. SLR combined: 18.2%/80.1%; CT-only: 14.7%/71.3%; ICT+CCRT: 24.2%/88.5%, respectively). The naïve indirect treatment comparison to state-of-the-art therapy indicated that P-32 microparticles combined with standard-of-care chemotherapy may provide significant and clinically relevant benefits for patients with unresectable LAPC and a valuable treatment option in an area of high unmet medical need.