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

Abstract

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.

Intratumoral injection therapies for locally advanced pancreatic cancer: systematic review

“…32 P was only injected percutaneously with CT guidance and achieved a tumour dose between 1255 and 19 000 Gy 58 , 59 , 61 . This dose was a notably higher dose than the dose of 100 Gy achieved by the more recent microparticle brachy­therapy utilizing EUS application 24 , 60 .…”

“…The authors also found the highest complication rate, with 75 greater than or equal to grade III complications in 16 of 18 patients (89 per cent) 58 , followed closely by Ross et al . 24 (2021) with 139 greater than or equal to grade III complications in 34 of 42 patients (81 per cent). In contrast, Ross et al .…”

“…Gemcitabine-based chemotherapy was the most frequently used form of induction/palliative chemotherapy. One study combined intratumoral injection therapy with FOLFIRINOX chemotherapy 24 . All results are presented per modality and an overview of all intratumoral injection therapies is presented in Table 1 .…”

“…One study included 19 patients (40 per cent) with stage IV pancreatic cancer 59 . The remaining studies had no patients with metastases (total 14.3 per cent) 24 , 58 , 60 , 61 . 32 P was only injected percutaneously with CT guidance and achieved a tumour dose between 1255 and 19 000 Gy 58 , 59 , 61 .…”

“…Some 61 patients (49.2 per cent) suffered from greater than or equal to grade III complications. The most frequently reported complications included haematological toxicities 24 , 58–60 , gastrointestinal haemorrhage 58 , 61 , fatigue 24 , 58 , and nausea 24 , 58 . The median OS of all five studies ranged from 5.2 months 58 to 15.5 months after inclusion 24 .…”