Survival Benefit Shown With IA Gemcitabine in Patients with Locally Advanced Pancreatic Cancer

Image Credit: © LASZLO -www.stock.adobe.com

Prolonged progression-free survival (PFS) has been demonstrated with intra-arterial (IA) administration of gemcitabine (RenovoGem) in patients with locally advanced pancreatic cancer (LAPC), according to interim findings from the pivotal phase 3 TIGeR-PaC study (NCT03257033).¹

Results presented during the 2023 European Society of Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer showed that in 23 patients, the median 8-month PFS was 15 months with RenovoGem compared with 7 months with the standard of care combination of gemcitabine plus nab-paclitaxel. In terms of overall survival (OS), the primary end point of the study, RenovoGem achieved a median OS of 16 months vs 10 months with gemcitabine/nab-paclitaxel. The OS results excluded roughly 5.5 months of life from the time of diagnosis to randomization during the induction chemotherapy and radiation phase of the study, according to a press release by RenovoRx.

Safety results from TIGeR-PaC showed that a greater than 65% reduction in adverse events occurred in the experimental arm compared with the control arm.

"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 support that RenovoGem has the potential to more than double progression-free survival compared to systemic chemotherapy alone in this difficult-to-treat cancer, which demonstrates support for a new treatment standard," said Michael J. Pishvaian, MD, PhD, director of gastrointestinal, developmental therapeutics and clinical research Programs and associate professor of Oncology,in a press release. "[These] data [have] the potential to be a paradigm-shifting treatment for patients at risk of cancer progression, including those who have limited well-tolerated options."

In TIGeR-PaC, a total of 330 patients with LAPC were randomized. In the experimental arm, patients received IA gemcitabine 1000 mg/m2 administered bi-weekly for up to 8 treatments, lasting approximately 16 weeks. In the control arm, patients were treated with IV gemcitabine 1000 mg/m2 over 30 minutes with nab-paclitaxel 125 mg/m2 over 30 minutes on days 1, 8, and 15 of a 28-day cycle.²

In addition to OS and the key secondary end point of PFS, the study explored objective response rate, health-related quality of life, neuropathy assessment, frequency of neutropenia, patient-reported symptoms, and safety as secondary end points.

Patients involved in the study were those with histologically or cytopathology confirmed LAPC, and an ECOG performance status of 0 or 1, adequate laboratory values at baseline and a life expectancy of > 12 weeks. All patients enrolled must have agreed to at least 8 months of participation in the study. Women in the study were required to produce a negative pregnancy test and use contraception during the study.

Patients were excluded from TIGeR-PaC if they were previously treated for pancreatic cancer, had prior anti-cancer therapy, oral or IV antibiotics for an infection within 2 weeks prior to study treatment, contraindications for stereotactic body radiation therapy, or underwent certain procedures before study treatment started. The study also excluded individuals with metastasis, HIV or active viral hepatitis, severe infections within 4 weeks of study treatment, cardiovascular disease, and other severe concurrent disease, or comorbidities which may interfere with a patient’s study participation.

"The TIGeR-PaC study results reinforce the intended clinical advantage that TAMP brings to pancreatic cancer treatment, versus the non-targeted approach of the current standard of care IV therapy," said Ramtin Agah, MD, chief medical officer, RenovoRx, in the press release.1 "The first look at interim analysis data of our pivotal trial supports this important advantage in overcoming the barrier of solid tumors in resisting drug uptake."

_REFERENCES:

_{1. RenovoRx announces new positive interim phase III data demonstrating RenovoGem™ delays cancer progression by eight months in locally advanced pancreatic cancer. News release. RenovoRX, Inc. June 29, 2023. Accessed July 5, 2023. https://tinyurl.com/4sdvp3bh}

_{2. Intra-arterial gemcitabine vs. iv gemcitabine and nab-paclitaxel following radiotherapy for LAPC (TIGeR-PaC). ClinicalTrials.gov. Updated February 25, 2022. Accessed July 5, 2023. https://tinyurl.com/2xnj8sfr}