Intra-Arterial Gemcitabine for Patients With Locally Advanced Pancreatic Cancer

Key Clinical Summary: 

• Design/Context: The phase 3 TIGeR-PaC trial evaluates intra-arterial gemcitabine following induction chemotherapy and radiation in patients with locally advanced pancreatic cancer.
• Key Points: The study aims to test whether high-concentration, localized delivery of gemcitabine to the primary tumor can improve outcomes compared with continued systemic therapy.
• Clinical Relevance: TIGeR-PaC reflects ongoing efforts to incorporate local treatment strategies alongside chemotherapy to improve survival in a population with limited curative options.

Michael Pishvaian, MD, PhD, Johns Hopkins University, Baltimore, Maryland, discusses the phase 3 TIGeR-PaC study evaluating intra-arterial gemcitabine among patients with locally advanced pancreatic cancer. 

Dr Pishvaian discusses the rationale for combining systemic chemotherapy with targeted intra-arterial delivery to the primary tumor to enhance local tumor control and potentially improve overall survival in this patient population. 

Transcript:

My name is Mike Pishvaian, I’m a GI medical oncologist, particularly focused on pancreatic cancer at Johns Hopkins University. I’m here to talk today about the TIGeR-PaC study for locally advanced pancreatic cancer.

Locally advanced pancreatic cancer represents about 30% of all new pancreatic cancer diagnoses so it’s a big problem and there are no definitively set guidelines for how we treat this disease. For the most part, we know that patients with locally advanced pancreatic cancer typically cannot be rendered surgically operable and thus curable so we’re mostly treating these patients with the goal of trying to extend survival and improve quality of life. 

We do that with the same chemotherapeutic regimens that we use for metastatic disease including FOLFIRINOX, NALIRIFOX, and gemcitabine/nab-paclitaxel. However, for many years, we as a global community have been trying to explore whether local therapies can improve outcomes for patients with locally advanced pancreatic cancer, which makes logical sense because you’re dealing primarily with disease in the pancreas that has wrapped itself around the blood vessels. While there is micrometastatic disease, addressing the primary tumor can be really important. 

The hard reality is that there has been no definitive local therapy, until recently, that has been proven to help patients with locally advanced pancreatic cancer. Most notably, there have been several large studies of radiation therapy over the last 10 to 15 years all of which have been negative, at least in terms of improving overall survival. 

We did recently get our first glimpse that perhaps local therapy can actually help survival through the use of tumor treating fields, a device that delivers electrical stimuli, and was shown to improve median overall survival in this population. It really set the paradigm that perhaps treating the primary disease, in addition to micrometastatic disease with chemotherapy, can improve survival. In that context, we launched the TIGeR-PaC  study.

The TIGeR-PaC study utilizes a device, a dual-balloon catheter, in which interventional radiologists can access the artery most proximal to the tumor, they can inflate 2 balloons, and deliver a high concentration of gemcitabine very locally to the tumor. There have been elegant animal model studies showing that the concentration of gemcitabine delivered to the tumor can be much, much higher—on the order of a thousand-fold higher—than what is achieved systemically, with fewer systemic side effects since it is not given intravenously. There was an initial phase 1 study demonstrating the safety of intra-arterial gemcitabine. Additionally, survival outcomes in that study appeared promising, particularly in patients who had received prior radiation therapy. The thought is that prior radiation to the tumor and its microvasculature may make tumors more susceptible to intra-arterial gemcitabine. 

With that background, we launched a nationwide phase 3 trial to evaluate whether intra-arterial gemcitabine can improve outcomes for patients with locally advanced pancreatic cancer, with overall survival as the primary end point. In this study, patients with locally advanced pancreatic cancer, strictly defined by NCCN guidelines, are enrolled. They receive 2 months of induction therapy with gemcitabine/nab-paclitaxel, followed by radiation therapy, based on the belief that this may presensitize tumors to intra-arterial therapy. After radiation, patients receive 1 additional month of gemcitabine/nab-paclitaxel, for a total of about 4 to 5 months of induction therapy.

Patients are monitored during this time, and those without disease progression are then randomized 1:1 to either receive intra-arterial gemcitabine, administered every 2 weeks for up to 8 treatments, or to continue standard-of-care gemcitabine/nab-paclitaxel with appropriate dose modifications. After approximately 4 months of treatment in either arm, patients may continue therapy or transition to maintenance, including the option of oral capecitabine, depending on physician preference. Patients are then followed for overall survival.

The primary end point is overall survival, with the hypothesis that intra-arterial gemcitabine will improve median overall survival in this population. This trial is actively enrolling across the country and is nearly complete with accrual. We expect enrollment to finish in the coming weeks, with overall survival data anticipated in 2027. Keep an eye out, this should be a very exciting study.

Source: 

RenovoRx. RenovoRx announces key phase III milestone: TIGeR-PaC Trial surpasses 100 randomized patients as study nears completion of enrollment. https://ir.renovorx.com/news-events/press-releases/detail/154/renovorx-announces-key-phase-iii-milestone-tiger-pac-trial