Results of a single-arm pilot study of 32 P microparticles in unresectable locally advanced pancreatic adenocarcinoma with gemcitabine/nab-paclitaxel or FOLFIRINOX chemotherapy.

Autor:	Ross PJ; Guy's & St Thomas' Hospital NHS Foundation Trust, London, UK. Electronic address: paul.ross@gstt.nhs.uk., Wasan HS; Imperial College Healthcare NHS Trust, London, UK., Croagh D; Monash Health, Clayton, Australia., Nikfarjam M; Austin Hospital, University of Melbourne, Australia., Nguyen N; Royal Adelaide Hospital, Adelaide, Australia., Aghmesheh M; Southern Medical Day Care Centre, Wollongong, Australia., Nagrial AM; The Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, Australia., Bartholomeusz D; Royal Adelaide Hospital, Adelaide, Australia., Hendlisz A; Institut Jules Bordet, Brussels, Belgium., Ajithkumar T; Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Iwuji C; Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, UK., Wilson NE; OncoSil Medical Limited, Sydney, Australia., Turner DM; OncoSil Medical Limited, Sydney, Australia., James DC; OncoSil Medical Limited, Sydney, Australia., Young E; Southern Star Research Pty Ltd, Gordon, Australia., Harris MT; Monash Health, Clayton, Australia.
Jazyk:	angličtina
Zdroj:	ESMO open [ESMO Open] 2022 Feb; Vol. 7 (1), pp. 100356. Date of Electronic Publication: 2021 Dec 23.
DOI:	10.1016/j.esmoop.2021.100356
Abstrakt:	Background: Unresectable locally advanced pancreatic cancer (LAPC) is generally managed with chemotherapy or chemoradiotherapy, but prognosis is poor with a median survival of ∼13 months (or up to 19 months in some studies). We assessed a novel brachytherapy device, using phosphorous-32 ( 32 P) microparticles, combined with standard-of-care chemotherapy. Patients and Methods: In this international, multicentre, single-arm, open-label pilot study, adult patients with histologically or cytologically proven unresectable LAPC received 32 P microparticles, via endoscopic ultrasound-guided fine-needle implantation, planned for week 4 of 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) or gemcitabine/nab-paclitaxel chemotherapy, per investigator's choice. The primary endpoint was safety and tolerability measured using Common Terminology Criteria for Adverse Events version 4.0. The lead efficacy endpoint was local disease control rate at 16 weeks. Results: Fifty patients were enrolled and received chemotherapy [intention-to-treat (ITT) population]. Forty-two patients received 32 P microparticle implantation [per protocol (PP) population]. A total of 1102 treatment-emergent adverse events (TEAEs) were reported in the ITT/safety population (956 PP), of which 167 (139 PP) were grade ≥3. In the PP population, 41 TEAEs in 16 (38.1%) patients were possibly or probably related to 32 P microparticles or implantation procedure, including 8 grade ≥3 in 3 (7.1%) patients, compared with 609 TEAEs in 42 (100%) patients attributed to chemotherapy, including 67 grade ≥3 in 28 patients (66.7%). The local disease control rate at 16 weeks was 82.0% (95% confidence interval: 68.6% to 90.9%) (ITT) and 90.5% (95% confidence interval: 77.4% to 97.3%) (PP). Tumour volume, carbohydrate antigen 19-9 levels, and metabolic tumour response at week 12 improved significantly. Ten patients (20.0% ITT; 23.8% PP) had surgical resection and median overall survival was 15.2 and 15.5 months for ITT and PP populations, respectively. Conclusions: Endoscopic ultrasound-guided 32 P microparticle implantation has an acceptable safety profile. This study also suggests clinically relevant benefits of combining 32 P microparticles with standard-of-care systemic chemotherapy for patients with unresectable LAPC. Competing Interests: Disclosure PJR: stock and other ownership interests: Perci Health Ltd. Honoraria: Sirtex Medical, Eisai, Servier, Pierre Fabre, Shire, Roche, AstraZeneca, Merck. Consulting or advisory role: Sirtex Medical, Eisai, Servier, Roche, AstraZeneca, Amgen. Speakers’ bureau: Amgen, Merck, Servier, Boston Scientific. Research funding: Sanofi, Bayer. Travel, accommodations, expenses: Roche, Ipsen. HSW: honoraria: BTG/Biocompatibles, Merck KGaA, and BMS. Consulting or advisory role: Incyte, Bayer, Roche/Genentech/ Foundation Medicine, Sirtex Medical, Celgene, OncoSil Medical, and Zymeworks. Research funding: Pfizer, Sirtex and Zymeworks. Travel, accommodations, expenses: BTG/Biocompatibles, Merck KGaA, and BMS. DC: stock and other ownership interests: MarginClear. Consulting or advisory role: Boston Scientific and OncoSil Medical. Research funding: Boston Scientific. MN: stock and other ownership interests: Pakinax Pty Ltd and Margin Clear Pty Ltd. DB: employment: SA Medical Imaging and SA Health. Research funding: Avener/Pankind and AstraZeneca. NEW: employment: OncoSil Medical Ltd. Stock and other ownership interests: OncoSil Medical Ltd. DMT: employment: OncoSil Medical Ltd. Stock and other ownership interests: OncoSil Medical Ltd. DCJ: employment: OncoSil Medical Ltd. Stock and other ownership interests: OncoSil Medical Ltd. EY: employment: Southern Star Research Pty Ltd (contractor to OncoSil Medical Ltd). All other authors have declared no conflicts of interest. (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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