A New Approach Runs the Table for Early Colorectal Cancer
The use of immunotherapy led to a 100% response rate in a very small study of a colon cancer subtype (MMR-deficient tumors).
This year, in the USA alone, we will see more than 100,000 new cases of colon cancer. There will be an estimated more than 44,000 new cases of rectal cancer, according to the American Cancer Society. Many patients will receive chemotherapy in addition to surgery, and selected patients with rectal cancer may also have radiation therapy. Today, we turn to an interesting twist in the management story.
Beyond chemotherapy alone, and into the future
Decades of research. Scores of clinical trials. Nobel Prizes. Immunotherapy uses the body’s own immune system to fight cancer. This management approach involves the stimulation of the immune system to help it do its job more effectively. Recently, so-called checkpoint inhibitor drugs unleash the immune response against cancer cells.
Wikipedia offers that checkpoint inhibitor therapy (including PD-1 inhibitors such as nivolumab or Opdivo) “targets immune checkpoints, key regulators of the immune system that, when stimulated, can dampen the immune response to an immunologic stimulus. Some cancers can protect themselves from attack by stimulating immune checkpoint targets. Checkpoint therapy can block inhibitory checkpoints, restoring immune system function.”
With tremendous research efforts, immunotherapies have moved to the forefront to help those with many types of advanced cancer. More recently, we see a move of these drugs into earlier disease. Today, I bring you more good news about the management of early, operable colon cancer.
For the NICHE study, researchers recently enrolled forty patients with operable localized colorectal cancer. Thirty-five could be evaluated for a response, including twenty with so-called dMMR tumors (more on that in a bit)and 15 with pMMR cancers. All received a single dose of the immunotherapy ipilimumab and two doses of the immunotherapy nivolumab prior to surgery. Selected patients also received a non-steroidal anti-inflammatory (NSAID) drug known as celecoxib.
Now it gets more exciting. For those with a mismatch repair-deficient (dMMR) colorectal cancer, there was a response to the drugs. In every single case. All but one had a complete pathological response (no cancer, or 10 percent of less residual) found at surgery. For those with a mismatch repair-deficient (dMMR) colorectal cancer, there was a response to the drugs, in every single case.
Oddly, historically those with cancer without the mismatch repair deficiency, who had spread to distant sites, did not seem to respond to this immunotherapy approach.
Potentially practice changing?
We need more follow-up to determine whether we should use immunotherapy for early-stage colon cancers (prior to surgery). If confirmed in larger studies with longer follow-up, we may have a new standard of cancer for those with mismatch repair deficient colon cancer, and perhaps even selected patients who do not have this deficiency.
Will the remissions be long-lived? Did the addition of celecoxib, a COX-2 inhibitor drug, change tumor-producing inflammation (in turn leading to better immunotherapy responses)? The treatments appeared to be well-tolerated, and all patients had surgery within the pre-defined six-week interval after inclusion in the study.
An additional question is this: While the drugs appeared to work quite well for early disease, does it have the same effect on any cells that have escaped into the bloodstream? In other words, is early-stage colon cancer very different from advanced-stage disease? The early disease has a rich blood supply, and may have a nice response of the immune system to it; does the micrometastatic (small bits of cancer that have metastasized, or escaped to distant organs such as the liver, lung, or bone) disease too?
Historically, these checkpoint immunotherapy agents have not shown much activity for advanced colorectal disease. Traditional chemotherapy may still play an important role in the management of early colorectal cancer. I look forward to seeing larger, randomized studies with longer follow-up to get a real sense if immunotherapy is a game-changer for early colorectal cancer. Still, I have hope.
What is MSI-H/dMMR?
Oh, one more thing. Microsatellite instability-high/deficient mismatch repair (MMR-deficient cancer) is an indicator of instability of the gene. This is an indicator of instability of a gene. Patients with MSI-high/dMMR have an increased number of mutations in a tumor. This may be associated with an increased immune system (T-cell) activation, and how immune cell infiltration of tumors may be associated with response to therapy.
I’m Dr. Michael Hunter
- Checkpoint inhibitor — Wikipedia. https://en.wikipedia.org/wiki/Checkpoint_inhibitor