Immunotherapy before surgery may lead to better outcomes

The main treatment for colon cancer is surgery, but a study published this week showed New England Journal of Medicine Scientists have found that two immunotherapy drugs administered before surgery significantly reduce the size of tumors without raising any serious safety concerns.

The researchers decided to study the safety profile of the drugs by observing whether patients taking them were able to undergo surgery within the designated time frame or had to postpone surgery. Approximately 98% of patients underwent surgery as scheduled, meaning the surgery was postponed by less than two weeks after taking the drug combination.

The researchers observed immune-related side effects in 73 patients, of which five patients experienced serious (grade 3 or 4) events. No patients discontinued treatment due to these adverse events.

The drug's effect on the tumors themselves was also remarkable: the study found that 95% of patients had a major pathological response, with their tumors shrinking by less than 10%, while two-thirds of patients had a complete pathological response, with no trace of tumor remaining after treatment.

More than two years after surgery, no patients have experienced a recurrence of their cancer, and they are being followed up for a longer period to assess the durability of their responses.

“I don't think anybody expected this outcome or the extent of this outcome.” Dr. Kristen Chambers, “These findings are important to our understanding of the condition, and we are looking at ways to prevent it,” an associate professor of medicine at Vanderbilt University Medical Center who was not involved in the study told Healthline.

“Two-thirds of patients had no tumor remaining, which is truly remarkable – a rate and extent that has rarely been seen with other treatments,” she said.

The study, conducted by researchers in the Netherlands, involved 115 patients with nonmetastatic, locally advanced, previously untreated dMMR colon cancer — a technical term for colon cancer that has progressed past an early stage (the patients in the study had stage II or II cancer) but hasn't yet spread to other organs in the body (metastasized).

Before the surgery, doctors administered two types of immunotherapy drugs to the patient. Nivolumab and Ipilimumabbelongs to the same class of immunotherapy treatments, Immune checkpoint inhibitorseach utilizing its own biological mechanisms.

“The greatest advances in cancer research over the decades have been in the field of immunotherapy. Developing immunotherapies to help the immune system attack cancer is something we've dreamed of since the 1950s.” George Fisher“These findings are a major contributing factor to the decline in patients with rheumatoid arthritis,” MD, professor of medical oncology at the Stanford University School of Medicine, told Healthline.

The results of this latest trial show how far the field has come.

The concept of immunotherapy is simple to explain, but extremely complex to implement. When the body mounts an immune response, it needs to distinguish between friendly cells and foreign invaders. To do this, T cellsImmunoglobulins, the body's defenders in the immune response, act like a “handshake.” Immune CheckpointsIt lets healthy cells recognize it as safe, and without it, the T cells will attack.

Certain cancers can exploit this mechanism to hide from the immune system, allowing them to continue growing without fear of an immune response.

Immune checkpoint inhibitors work by preventing cancer cells from faking this “handshake,” allowing the immune system to identify and kill the cancer cells.

To further complicate things, colon cancers in particular tend to remain hidden from detection by the immune system. But dMMR is different: the genetic mutations characteristic of dMMR make it easier for the immune system to detect and more susceptible to immunotherapy.

“The more mutations you have, the more abnormal proteins you have, and if the immune system can recognize abnormal proteins, the cells with the most mutations are the ones most likely to have proteins that can be recognized as foreign,” Fisher said.

“The genetic mutations in these tumors make them what we call 'immunologically hot,' so immunotherapy can work more effectively against the tumor itself,” Siomboll said.

Experts interviewed by Healthline said that much work still needs to be done to know whether the immunotherapy used in this study is safe and effective in a larger group of patients, but the results are intriguing nonetheless.

“There's no doubt this study is very impressive, and the fact that we can see such large changes in such a short period of time with treatment with both drugs suggests that there is likely a group of patients who don't need to undergo surgery,” Fisher said.

If clinical trials continue to show safety and efficacy, immunotherapy may provide new options for certain patient groups: for example, older patients or those with certain comorbidities who are not suitable for surgery may be able to opt for it.

Patients with low-grade cancer may choose to forgo surgery, but the long-term outcomes of immunotherapy without surgery have yet to be established.

As with any treatment, there are risks and benefits. Immunotherapy before surgery may eliminate the need for chemotherapy, The risk of serious complications called immunotherapy toxicity.

“It at least raises the possibility that there may be other options for treating this type of cancer,” Siomboll said.

“If we can avoid chemotherapy, that's a win. And ultimately if we can avoid surgery as well, that would be really great. But we can't draw that conclusion from this study yet. That's a bit of a stretch,” she said.

In a study of more than 100 patients, a two-drug immunotherapy has shown impressive results in treating a certain type of colon cancer.

Mismatch repair deficient (dMMR) colorectal cancer accounts for 10-15% of all colorectal cancer cases and is characterized by a large number of gene mutations.

These genetic mutations may make the tumor more easily recognised by the immune system, making immunotherapy more effective.