Irreversible Electroporation Plus Anti-PD-1 Antibody versus Irreversible Electroporation Alone for Patients with Locally Advanced Pancreatic Cancer

Abstract

Background Irreversible electroporation (IRE) is shown to not only improve the prognosis of patients with locally advanced pancreatic cancer (LAPC) but also activate the immune system. Considering the immune-activating function of IRE, IRE may enhance the effect of immune checkpoint inhibitors in the treatment of LAPC. We aimed to compare the effect and safety of IRE combined with toripalimab versus IRE alone for LAPC. Methods We retrospectively collected data from LAPC patients treated with IRE plus toripalimab (240mg, 7 days after IRE) or IRE alone at Sun Yat‑sen University Cancer Center. Overall and progression-free survival and treatment-related adverse events were evaluated and compared. Results From August 2015 to June 2020, a total of 85 patients were collected and analyzed in this study: 70 in the IRE group and 15 in the IRE plus toripalimab group. The IRE plus toripalimab group showed longer OS [44.33 months (95% CI 17.39–71.27) versus 23.37 months (95% CI 21.20–25.54), P=0.010] and PFS [27.5 months (95% CI not reached) versus 10.6 months (95% CI 7.79–13.42), P=0.036], compared with IRE group. There were no treatment-related deaths in all patients of this study. Although pancreatic fistula, biliary fistula, abscess, vomiting and gastroparesis were a little more common in IRE plus toripalimab group, no significant differences in the rates of all adverse events between these two groups were observed. Conclusion IRE plus toripalimab had acceptable toxic effects and might improve survival in LAPC compared with IRE alone.

Electroporation and Immunotherapy—Unleashing the Abscopal Effect

“…One prospective trial of 10 patients with locally advanced pancreatic cancer treated with IRE + anti-PD-1 showed a median OS of 18 months [ 140 ]. This contrasts with a retrospective study of IRE + anti-PD-1, which showed a median OS of 44 months in locally advanced pancreatic cancer [ 141 ]. Small sample sizes and different study designs make the studies difficult to compare; however, the retrospective study did show a superior OS in the IRE + anti-PD-1 group versus IRE alone (median OS 44 months vs. 23 months, respectively).…”

Local Ablative Therapy Associated with Immunotherapy in Locally Advanced Pancreatic Cancer: A Solution to Overcome the Double Trouble?—A Comprehensive Review

“…Of note, the statistically significant differences occurred at 3 months postoperatively, following the completion of immunotherapy. In a study by He et al [ 84 ], the number of CD4 + ( p = 0.038) and CD8 + ( p = 0.024) T cells increased while that of CD8 + Treg cells ( p = 0.023) decreased in the IRE plus toripalimab treatment group compared with those in the IRE-only treatment group.…”

“…Except patients in the Pan [ 81 ] study who were not pre-treated, half of the patients underwent previous chemotherapy treatment with gemcitabine [ 82 , 83 ] and nab-paclitaxel [ 73 , 83 , 84 ] or FOLFIRINOX [ 73 , 82 , 83 , 84 ] in various ratios.…”

“…To date, there are only two published trials with checkpoint inhibitors [ 73 , 84 ], with one trial involving a total of 25 patients with unresectable PDAC. The combination of IRE and the anti-PLD1 [ 73 ] antibody nivolumab was given successfully without any dose reduction (nivolumab 240 mg).…”

“…Survival was not compared. The other study [ 84 ] used the anti-PD1 Toripalimab (240 mg) with acceptable toxic effect and found a benefit compared with IRE alone on PFS (27.5 vs. 10.6 months, p = 0.036) and OS (44.3 vs. 23.4, p = 0.010). One of the study aims from O’Neil et al [ 73 ] was to evaluate the establishment of memory T cells after nivolumab treatment associated with IRE.…”