Immunotherapy Combination ‘Huge Benefit’ for Some Patients With Colorectal Cancer

A combination of two immunotherapy drugs — botensilimab and balstilimab — demonstrated clinical activity in patients with refractory metastatic colorectal cancer, a patient population with few treatment options available, according to recent study results.

“It’s a huge benefit for patients,” said Dr. Benjamin L. Schlechter, lead author on the study and senior physician at Dana-Farber Cancer Center in Boston, in an interview with CURE®. “It's a huge benefit because the people who get this drug may actually derive substantial disease control. Not only that, (but) this may help us understand how to treat colon cancer with immune therapy and that's been really completely lacking. We really don’t know how to treat colon cancer with immunotherapy.”

Immune checkpoint inhibitors, such as the ones assessed in this trial, are drugs that treat the immune system itself rather than the cancer directly. And what they do is “shield the immune system” from the cancer, according to Schlechter, so it cannot be injured. Instead, the therapy can identify the cancer and kill it, he explained. And although this has been effective in other cancers, it has not been shown as such in colon cancer until this trial.

“As a class, these drugs have never really reliably worked in more common colon cancer types, and this is the first time that’s happened,” he said.

The phase 1 trial, which was presented at the 2023 ASCO Gastrointestinal Cancers Symposium, included 70 patients with metastatic colorectal cancer who had been previously treated with several lines of therapies, including other immunotherapies.

At a median follow up of seven months, 23% of patients had a reduction in the size of their tumor. Disease control rate (the percentage of patients whose metastatic disease had a complete or partial response to therapy and remained stable) was 76%. Additionally, the 12-month overall survival (when a patient with cancer is still alive during a given period of time) was 63%. Of note, those without active disease in the liver benefited the most from the combination.

“This looks like the beginning of immune therapy in colorectal cancer, which is really, really important,” he noted. Schlechter explained that this is a patient population who have very few treatment choices and may not respond well to therapies that are available.

When colorectal cancer recurs after surgery, the main treatment becomes chemotherapy, which Schlechter called “reasonably effective and reasonably tolerated.” The next treatment option after chemotherapy are pills, but typically only 2% to 6% of patients benefit from these, he explained. So, Schlechter noted, there has been a search for better options for this patient population.

“It's not that we want these drugs; it’s that they're the best we've got,” he said. “And so the race has been on to find drugs better than (these). The other race that's been on is the race to identify immune therapies that can work in colon cancer, because in general, for colon cancer, immune therapy is ineffective.”

And the race continues, as there are now later-stage trials either being initiated or in the works, including a phase 2 trial which will evaluate the most effective dosage of the therapy and compare the combination to other drugs in the space.

“The way it will benefit patients is the drugs seem to work in the phase 1 trial with all the caveats in place,” he concluded. “And we may now have finally sort of opened the box on how to treat these patients because before this, it's been a closed box, we can't see inside and we don't know why colon cancer has been so hard to treat.”

Side effects were reported in 91% of patients with 40% considered severe or worse and 3% considered life threatening. In addition, 12% of patients discontinued the combination therapy due to side effects. Schlechter added that these side effects were expected and manageable.

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