Clinical Trials Enhance Care for Advanced Gastrointestinal Cancers

According to Dr. Michael J. Pishvaian, clinical trials improve care and access to novel treatments for advanced gastrointestinal cancers.

Clinical trials offer more than just access to novel treatments — they provide patients with comprehensive care and closer monitoring, according to Dr. Michael J. Pishvaian of Johns Hopkins Kimmel Cancer Center. His experience leading trials across all phases underscores how participation can improve outcomes and drive progress in gastrointestinal (GI) cancer research.

Pishvaian sat down with CURE and highlighted emerging therapies for advanced GI cancers, including liver-directed treatments and precision medicine approaches. He explains how multidisciplinary planning and biomarker testing are reshaping patient care, especially in colorectal and pancreatic cancers.

Pishvaian is based at Sibley Memorial Hospital in Washington, D.C. He is the director of Gastrointestinal, Developmental Therapeutics and Clinical Research Programs for the Johns Hopkins Kimmel Cancer Center in the Greater Washington Area and an associate professor at the School of Medicine.

What are the key benefits of participating in a clinical trial for GI cancer, and how does your expertise in conducting all phases of trials ensure patient safety and access to cutting-edge treatments?

I always encourage patients to go on clinical trials, not just because I'm trying to enroll them in a clinical trial, but we have a few benefits that are a little bit more subtle, if you will. Not least of which is the fact that when patients are enrolled in clinical trials, they are watched much more closely. They typically have multiple study members that are involved in their care. And we know actually, studies have shown that patients actually have better outcomes when they're enrolled in a clinical trial, because they have more eyes on them, if you will, taking care of their cancer.

Of course, there's the most basic level that many of our drugs that are being tested, the novel therapies in particular, are only available in clinical trials. I keep going back to the KRAS inhibitors. It's been incredibly frustrating that none of them are [Food and Drug Administration (FDA)] approved yet. So we are clawing and scratching and begging for slots to be able to put our patients on these clinical trials, quite frankly, anywhere in the country that they can get a slot. So sometimes it's just strictly an access question as to why we want to do clinical trials.

But then the other thing for clinical trials is that we do learn from trials, even if the drug doesn't work for the group of patients. So there may be a trial that enrolls 100 patients, and for 97 of the patients it doesn't work, but for three of the patients it does, and investigating why it helped those three patients can sometimes be transformational.

In fact, there's a class of drugs in lung cancer. I'll borrow from my lung cancer colleagues; there's a class of drugs that was intended for a certain type of biomarker called C-MET. It didn't work at all, but they realized that the few patients for whom it worked, it worked amazingly well. And it turned out that those patients had a specific fusion gene called an ALK fusion, for which the drug worked amazingly well, and that really opened up a whole new door for therapy for lung cancer.

So any clinical trial where these patients are being monitored very, very closely can be of benefits to the patient and to the population at large.

For patients with advanced or metastatic GI cancers, such as those that have spread to the liver or peritoneum, what are some of the most promising new treatment strategies beyond standard chemotherapy, and how do you determine which patients are candidates for these innovative therapies?

For liver-directed therapy, which is a big part of the care of GI cancers, this is something that we discuss all the time and particularly discuss in our multidisciplinary clinics and multidisciplinary tumor boards, because the truth is that we actually have many ways to go at tumors in the liver.

There's chemotherapy and other systemic therapies, of course. There's surgery as the true local therapy gold standard, where they're going after the tumor that they can see. The intervention radiologists have tools like radio frequency ablation, cryoablation, chemo embolization and radio embolization that get to the tumors in the liver directly through the artery.

There's a brand-new tool called histotripsy, which is an ultrasound-guided therapy, which is showing a lot of promise. And then finally, our radiation oncologist can aim radiation in a very focal way to tumors in the liver. And discussing this in an open forum, trying to decide what is the base best modality for any individual patient, is really the best way at going at each individual patient.

The peritoneum is an interesting discussion, because we as a group across the world have been debating whether there's any value to treating cancers within the peritoneal cavity for many, many years. There's surgery to remove the lining of the peritoneal cavity, something called a peritonectomy, with or without chemotherapy that gets injected into the into the abdominal cavity after the surgery. There are also techniques to try and just inject chemotherapy in the absence of surgery.

A lot of this is debated, and the answers are really unknown. In fact, I'll give you a perfect example, talking about [the American Society of Clinical Oncology (ASCO)] GI [conference]. There's been a kind of on-again, off-again approach for gastric cancer that has spread to the peritoneal cavity as to whether there's any value to treating the peritoneum. And most recently, it was off again, and we decided it wasn't worth it. And then there were two big presentations at ASCO GI in January, including a phase 3 trial out of China that said, “Oh, actually, you do see a survival benefit if you treat these patients.” And a lot of that was about selecting the right patients, those whose cancer was responding to chemotherapy and had low volume peritoneal disease. So I think continuing to explore these different, what we call local therapy techniques, and integrating them into the overall systemic therapy can be really important.

Could you explain how precision medicine helps tailor treatment plans for individual patients, and what specific advancements have you seen so far in this area for conditions like colorectal or pancreatic cancer?

I think precision medicine has really been transformational over the last 20 years for virtually all cancer subtypes. What we've been able to do is to carve a cancer type into multiple different subtypes. And again, lung cancer is the best example of this. There was a seminal paper in 2002 that came out that tested four different kinds of chemotherapy in lung cancer and in metastatic lung cancer, trying to decide which was the best. And there basically was no difference between any of them, and the average survival time was eight months for the whole group of patients, irrespective of what they got.

It was really not long after that that people started to understand that 10% to 15% of lung cancers are EGFR mutated, and then there were the ALK fusions, and then the ROS fusions, and all these tiny little subgroups of lung cancer started to become apparent. And as a result, you actually had very targeted therapies with survival times that are sometimes now measured in years, sometimes getting close to a decade for patients with otherwise incurable advanced lung cancer.

We're seeing similar progress in GI cancers as well. I mentioned a second ago MSI high colorectal cancer, where patients, even patients with metastatic disease that has spread, some of them are being cured with immunotherapy that's targeted for those patients with MSI high cancer. In pancreatic cancer, I would argue that the only progress that's been made in the last 10 years has really been in the biomarker subgroups of patients for whom we actually have directed therapies.

It really is incumbent upon us. In fact, a lot of my friends and colleagues have used the term malpractice, and I don't think that that's an unfair term to throw out there. That if we aren't testing our patients, at least those with advanced disease, for their genetic biomarkers, we are under serving them. That is malpractice, just by the definition. So we have to get to the point of virtually 100% testing rates to be able to benefit these patients.

Transcript has been edited for clarity and conciseness.

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