The ERASur trial

Learn about first-line trials with Dr. George

This blog series is about first-line trials by PALTOWN Scientific Director Dr. Manju George.

Earlier this week, I posted some general information about 1L clinical trials. you can find that post here: What are first-line trials?

In today’s post, I wanted to talk about one of those 1L trials.

Personally, I have a vested interest in this trial because it was designed with input from COLONTOWN. This is the ERASur trial.

Who is it for: Newly diagnosed metastatic (or stage 4) colorectal cancer patients with not as much wide spread disease.

You can skip to the links to watch the video (long or short) below if you don’t want to read this long post.

As we all know, there is a subset of metastatic colorectal cancer, where the patients have “oligometastatic disease.”

What the heck is that, you may ask?

“Oligo” means small, so oligometastatic means very few mets. These are patients who at diagnosis have 1 or 2 lung mets or 1 or 2 liver mets or a couple of distant enlarged lymph nodes. Once these are treated with local therapy — resection or ablation etc and the patient doesn’t develop any more mets, these patients have excellent outcomes. Many in this group are considered cured if they remain disease free for 5 years.

The issue is that this group of patients have been treated very differently based on who their doctor or care team is. Many oligometastatic patients are just put in the stage 4 bucket, considered terminal & only offered chemo for life. Some lucky oligometastatic patients are treated with local therapies in select cancer centers. But systematic data on their outcomes are seldom collected. So we don’t know what the outcomes are for the group, and others don’t get to learn from these experiences.

Also, not everyone with oligometastatic disease respond the same. A % of people seem to develop other mets and then don’t seem to have the same outcomes as those whose cancer does not return. So the PIs of the ERASur trial wanted to systematically look at, as part of a randomized trial, the role of local therapy and its impact on long term outcomes. They also wanted to expand the group of patients eligible for local therapy to find out what is the subset of patients that derive the most benefit from such an approach.

It is these questions they are trying to answer in the ERASur trial. You can watch this video to learn more.

ERASur trial: Local treatment options for limited stage IV CRC (2023)

Unfortunately, trials like this which apply to a subset of stage IV patients, and need collaboration from radiation oncologists, surgeons and interventional radiologists are hard to carry out as there are many moving pieces.

Patients need to be identified early, at the time of diagnosis and they need to understand what the trial involves and if this is a right fit for them.

Keeping a trial open & enrolling is very expensive for cancer centers and they want to open trials which have high rates of enrollment. So if they can only open a few trials, they choose the ones that they feel can find patients quickly. If it’s only for a certain subset of patients, who may not be as many, it does not make sense to keep such trials open, when they could be looking at other trials where they can enroll more patients. The cancer centers [as I understand] get paid per patient for NCTN (National Clinical Trials Network)-run trials, so keeping a trial that enrolls 2 patients in 3 months versus something that enrolls 2 patients in 2 weeks looks very different to them. They have to pay their trial staff and records people etc anyways. The other important calculation is that as this is an NCTN (National Clinical Trials Network, sponsored by the NIH)-run trial, the NCTN has limited amounts of money. If a trial isn’t enrolling as expected, they don’t want to support it. They would rather use that money on a different faster enrolling trial.

From the patient perspective–in my personal opinion***this is my personal opinion*** & I want to make this very clear–I am not trying to sway anyone to consider this particular trial, I will be covering a couple of 1L trials this month. I think it’s a shame if people don’t know all of the context and are not aware of this trial because it is a very well-thought out trial which can do a lot for the field.

For metastatic CRC patients, this is a trial is a significant one because it allows many more patients to have local treatments to take care of multiple mets in the liver, lungs & lymph nodes. At this time, most patients who have mets in more than one organ are not eligible for local therapy.

In addition, because this is a nationwide trial, it allows community oncologists at small clinics to collaborate with specialist surgeons, radiation oncologists and interventional radiologists at a larger cancer center. The vast majority of colorectal cancer patients are treated at smaller clinics or community cancer centers. What this trial does is it allows more patients to use these same collaborations outside the trial because now the community oncologist knows which surgeon or radiation oncologist or interventional radiologist has a lot of experience doing these treatments because they have personally worked with them as part of the trial. This helps build expertise in many places and expands networks making more treatments accessible to more patients all over the country. I love this trial because of this as well.

Another beauty of this trial is that if the patient is eligible for the trial and randomized to the local treatment arm, they can continue chemo with their own oncologist , but can get the local procedure (surgery, radiation or ablation done) at another center during a 90 day period after induction chemo. So this is a very patient-friendly trial designed by a very thoughtful team of clinicians.

But now the trial is struggling with enrollment. There was a similar trial in Australia, Dr. Jeanne Tie was the PI. They had to close it because they too struggled with enrollment. It makes me really sad that such trials which can improve patient care directly and indirectly have so much trouble enrolling. If the team does not enroll a certain number of patients by October, they will have to close the trial prematurely.

It’s a clinical trial, which means it is testing a combination of treatments, so it comes with its own risks. As is obvious, I’m not providing medical advice but sharing my perspectives on a trial I care very much about. Not everyone is eligible. But if you are a newly diagnosed metastatic colorectal cancer patient with a few mets in 2 organs, this is certainly a trial you can bring up with your care team.

Patients need to get 12 or more weeks of 1L chemo, and after this they need to have some residual volume of disease which can be treated locally. Patients can pre-register before they start treatment, but it is not necessary. They can enroll as they reach 12 weeks of 1L chemo based on their response to chemo on scans. If they don’t have disease progression after the initial chemo and have sites of disease that can be treated safely with surgery, ablation or radiation, then they are enrolled for the study. It is a randomized trial, which means you have a 50:50 chance of being in the local therapy arm versus the control arm, where you continue with chemo. You can learn the specifics of eligibility from the infographic below.

As you can see, only a select group of patients are eligible to pre-register. Not all pre-registered patients can proceed with the trial. If all their mets disappear after induction chemo, there’s nothing to treat locally. Many patients if they are on the control arm ( and can’t get local treatments) may not want to continue in the trial. For these patients there is no real difference in the treatments they would otherwise receive outside the trial, yet they may not want to be part of the trial.

I am writing all of this to try to bring to your attention a lot of things that may not rise to our level of attention as patients or caregivers because for us we just need the treatment that improves our outcomes.

Posted below is an infographic on ERASur. If you prefer to read a scientific paper on it, here’s the link: Alliance for clinical trials in Oncology (Alliance) trial A022101/NRG-GI009: a pragmatic randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer: evaluating radiation, ablation, and surgery (ERASur)