Intra-arterial gemcitabine bumps up survival in locally advanced pancreatic cancer

In patients with locally advanced pancreatic cancer, treatment with intra-arterial gemcitabine leads to better survival and safety outcomes compared with standard-of-care therapy with intravenous gemcitabine/nab-paclitaxel, according to the first interim analysis of the phase III TIGeR-PaC trial presented at ESMO GI 2023.

The analysis occurred after the 26th event in the trial, at which time 45 patients had been randomly assigned to either intra-arterial gemcitabine (8 treatments bi-weekly; n=23) or standard of care (4 cycles; n=22) over 16 weeks.

Thirteen deaths were reported in each treatment arm. Overall survival (OS), the primary endpoint, was about 5 months longer in the intra-arterial gemcitabine arm than in the standard-of-care arm (median, 15.7 vs 10.1 months; hazard ratio [HR], 0.48, 95 percent confidence interval [CI], 0.20–1.12; p=0.08). [ESMO GI 2023, abstract LBA-1]

Additional data showed that the intra-arterial gemcitabine arm also experienced gains in progression-free survival (PFS; median, 14.8 vs 6.7 months; HR, 0.55, 95 percent CI, 0.21–1.47).

Lead study author Dr Michael Pishvaian of Johns Hopkins School of Public Health, MacMillan Center for International and Area Studies, Yale University, New Haven, US, emphasized that all patients received induction therapy comprising 3 cycles of standard of care and 1 cycle of stereotactic body radiotherapy (33 Gy in 5 fractions) before randomization.

Thus, the median OS estimates did not include approximately 5.5 months of life from diagnosis to randomization during the induction chemotherapy and radiation phase of the trial, Pishvaian pointed out.

Notably, patients who received intra-arterial gemcitabine had 65 percent fewer adverse events compared with those who received standard of care, he added. This difference was driven by haematologic events, such as neutropenia and thrombocytopenia, with 15 percent of patients in the standard-of-care arm receiving colony-stimulating factor as opposed to 0 percent in the intra-arterial gemcitabine arm.

Pishvaian noted that the only events that occurred more frequently in the intra-arterial gemcitabine arm were related to the procedure, namely abdominal pain and nausea. Both events were mild and were quickly resolved.

In terms of tolerability, a greater proportion of patients in the intra-arterial gemcitabine arm than in the standard-of-care arm completed all 4 cycles of treatment without treatment modification (61 percent vs 23 percent).

Straight to the tumours

Trans-arterial micro-perfusion (TAMP) is a treatment platform that delivers gemcitabine directly to the tumour site. This way, the drug concentration to the targeted pathological site is significantly increased relative to intravenous administration.

Pishvaian and colleagues had postulated that the TAMP approach could enhance the therapeutic effectiveness of gemcitabine, minimize the systemic side effects commonly associated with the traditional intravenous administration, and improve patient outcomes in turn.

“Clinical practice has been waiting decades for a meaningful advancement in the standard of care for pancreatic cancer treatment, with less toxicity and better outcomes. The new data from the TIGeR-PaC interim results [show that intra-arterial gemcitabine] has the potential to more than double progression-free survival compared to systemic chemotherapy alone in this difficult-to-treat cancer,” Pishvaian said.

Intra-arterial gemcitabine could be “a paradigm-shifting treatment for patients at risk of cancer progression, including those who have limited well-tolerated options,” he added.

The investigator shared that TIGeR-PaC is ongoing and continues to accrue participants, with a second interim analysis after 52 events expected at the end of 2024.