Open Label Phase III TIGeR-PaC Interim Data Observes 6-Month Median Survival Benefit: RenovoGem (Intra-Arterial Gemcitabine) Versus IV Gemcitabine and Nab-paclitaxel for Pancreatic Cancer Treatment
By Michael Pishvaian, MD, PhD
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Locally advanced pancreatic cancer has its own challenges because we’re really focused on trying to treat the tumor where it lies within the pancreas, while also treating the systemic micrometastatic disease that almost certainly is there. It’s also not usually a situation where we’re trying to get the patient to the point of operability. Unfortunately, we know that at least 85% of patients with locally advanced, unresectable pancreatic cancer, as defined by classical NCCN definitions, will never get to the point of operability. So really, it’s about local control and systemic control. We traditionally will start with chemotherapy because, as we’re learning with most stages of pancreatic cancer, it’s really the systemic disease that causes the most problems. And with the two therapies that we have available to us, Gemcitabine, Paclitaxel, and Folfironox, we do actually have a pretty good success rate in achieving some level of systemic control. But the question really becomes, after you’ve had a period of systemic control, are there things that you can do to the primary tumor, whether it’s radiation therapy or other techniques to try and control the primary tumor as well? And of course, most importantly, if you do that, will it actually change the outcomes to date, we’ve never actually had any proof that adding local control modality improve the outcome for these patients. In fact, actually we’ve had several studies that have shown us that giving radiation therapy in conjunction with or sequenced with systemic therapy does not improve overall survival.
What are your thoughts on the TIGeR-PaC study’s interim analysis results?
The results of the TIGeR-PaC study are definitely very intriguing. It is an interim analysis, so we always have to take those with a grain of salt, but at the same time, an improvement of 6 months in overall survival is fairly remarkable for this stage of disease and where these patients are in their cancer journey. And I’m glad that the focus was really on meeting overall survival because when we’re talking about a study that’s assessing really a local modality. Then the ultimate question is it helping improve overall survival? Because as I mentioned, things like radiation therapy, which is also a local therapy, has unfortunately not been shown to improve overall survival. So if local therapy with this intra-arterial delivery system of gemcitabine is going to improve overall survival, that’s actually a meaningful change for these patients. Of course, we have to wait for the final results to see if that actually pans out.
If the RenovoGem study continues on this positive trend and meets its endpoints. How important will this data be to the oncology community?
If the data continues with this same trend, and the final overall survival analysis does show a significant improvement in overall survival. Then for a disease and a stage of disease where there really haven’t been any major changes since the implementation of the FOLFIRINOX and Gemcitabine, Paclitaxel now 12 years ago. This could be something that would be potentially practice changing. It would be a challenge to figure out how we’re gonna incorporate this in routine practice because it is a juxtaposition and interaction between the medical oncologist and the interventional radiologist, but in many centers there’s a growing group of interventional oncologists who are really focused on treating the cancer through different interventional radiology, different techniques that they have available to them. And I would definitely try and work with my interventional oncologist that we have here to maximize the timing and the schedule and the sequence to start to incorporate this kind of therapy for our patients with locally advanced unresectable pancreatic cancer.
Please share more on the importance of a successful oncologist and interventional radiologist collaborative working relationship.
Cancer treatment has really become multimodal in its behavior, and we know that surgeons and radiation oncologists and medical oncologists have worked together for many years to try and maximize treatment of a patient’s cancer. But there are new growing branches, and especially interventional oncology is one of them where we’re trying to incorporate treatment of the disease locally in certain areas of the body, and incorporate that with systemic therapy and even sometimes with radiation therapy and surgery. So I’ve had the good fortune of working with some of some really great interventional oncologists who will do techniques that try and treat the liver, try and treat the pancreas, try and treat the lungs with different local therapies to optimize overall control of the patient’s cancer. And so in this context, with these results of the TIGeR-PaC our interventional oncologist would be engaged in taking over the patient’s care during that period that they would be receiving intra-arterial therapy. And then we do a good job actually co coordinating with one another just through email, scheduling and discussions to say, okay, I’m done with this patient and her treatment for inter in arterial therapy, now we can move back on to in to IV therapy at the right time.
Do you see any challenges related to oncologist and interventional radiologists working together?
I think as a general rule, the challenge is not really with the teams working together, because most of them tend to have good communication. What I worry about is how applicable this is to the general community, and I’ve seen some of this in the interventional oncology field. Where only a group of interventional radiologists have been fully trained to be able to, for example, deliver radioembolization to deliver or other more advanced techniques. And so there will need to be a, an adoption usually at more specialty centers, but hopefully ultimately more widely adopted for interventional radiologists. Who have the experience, getting to the appropriate artery and using this kind of a balloon catheter technique to be able to deliver the intra-arterial chemotherapy.
How have the patients tolerated RenovoGem versus Abraxane and Gemcitabine in the study?
I have to be honest that I was a little skeptical at first that patients would be willing to accept getting a catheter procedure done every two weeks for up to 16 weeks. But actually I’ve been pleasantly surprised the patients actually, seem to tolerate this quite well. It’s done in a interventional radiology suite, so it’s done under very controlled circumstances with the minimal pain and sedation that’s given as well as needed. And actually patients have expressed that they prefer this over their weekly or every other week dose of chemotherapy. So it gives them a nice break to be off of the standard chemotherapy with less chemotherapy side effects. So I’ve been pleasantly surprised at going through the procedures and of course, certainly of the therapy itself. And in fact, the TIGeR-PaC study is measuring quality of life as a very important key outcome assessment for the TIGeR-PaC study. This will give patients and the investigators the opportunity to really see whether getting into our arterial therapy on a biweekly basis will impact their quality of life. And as I said, this may be a situation where surprisingly, despite getting stuck every two weeks with a catheter, their quality of life might actually be better not being on IV chemotherapy, but of course that’s what they’re trying to measure and demonstrate. And so we’ll wait and see what the data shows.
How does this data compare to what you have seen, historically, in patients with locally advanced pancreatic cancer?
Locally advanced pancreatic cancer is really a stage of cancer that has only been defined in the last maybe 10 or 15 years. If you look back to the early 2000s, and certainly before then, many of the patients with what we would now define as locally advanced unresectable pancreatic cancer, were lumped in with patients with metastatic pancreatic cancer in clinical trials. And so the outcomes were often grouped. I remember distinctly, it was actually probably the early 2000 teens that the NIH started to make a request that we separate these subgroups of patients because their outcomes are distinctly different. And now we see a fairly homogeneous outcome for patients with locally advanced pancreatic cancer, where they’re meeting overall survivals are somewhere in the range of 12 to 15 months better than patients with metastatic disease but unfortunately still way too short for this patient population. So if these results bear out for the TIGeR-PaC study, this could be something that would really push that level up into the 18 to even 20 month range. The 10 month versus 16 month overall survival that was seen in the interim analysis does not include the four months of induction therapy that the patients are getting. So essentially from the time of diagnosis, it’s really 14 versus about 20 months, and so if we are able to see in a large phase 3 study, a 20 month or even close to 20 month median overall survival for patients with locally advanced pancreatic cancer. That would definitely be an improvement over what we’ve seen over the past 10 or 20 years.
How important is it for eligible sites to offer patients the opportunity to participate in the TIGeR-PAC clinical trial?
We’re hopeful that this interim data will get physicians and patients more excited about participating and enrolling patients in the TIGeR-PaC clinical trial. There we’re expecting results to be out by 2024. Obviously, if enrollment picks up and we could report that out sooner, that’d be fantastic. But we’re hoping that the energy and the excitement about this interim analysis will lead to more patients wanting to participate in and hopefully getting treated as part of this study.
With positive outcomes, do you see any other tumor types where RenovoGem should be studied and could potentially make an impact?
The other thing that’s interesting is that if this study proves positive, ultimately it really will affirm the idea that delivering local therapy to a tumor can enhance the overall survival for patients even while they’re receiving integrated systemic therapy. And we’ve seen this in other cancer types, with for example, colon cancer and other cancers. But certainly this would open the door up to other cancers that perhaps couldn’t have been reset, including things like gallbladder cancers, or bile duct cancers and even lung cancers. There may be means to try and get this catheter around the appropriate artery that will enhance delivery of the chemotherapy to those tumors. So I think it really just opens the doors considerably to other tumor types that might be considered.
Michael Pishvaian, MD, PhD – About The Author, Credentials, and Affiliations
Michael Pvaian, MD, PhD is a renowned oncologist and researcher with expertise in gastrointestinal and pancreatic cancers. He currently serves as the Director of the Phase I Clinical Trials Program and the Medical Director of the Cancer Outcomes Research Program at the Georgetown Lombardi Comprehensive Cancer Center. Dr. Pishvaian has authored several publications in leading medical journals and has been a principal investigator in numerous clinical trials. He is a member of several professional organizations, including the American Society of Clinical Oncology and the American Association for Cancer Research. Dr. Pishvaian is known for his dedication to advancing cancer research and providing compassionate care to his patients.