A four-week course of dual immunotherapy prior to surgery is highly effective in treating a certain type of non-metastatic colorectal cancer, researchers at the Netherlands Cancer Institute in Amsterdam—the Antoni van Leeuwenhoek Hospital—found. Remarkably, the treatment proved effective for almost all patients, with tumors completely disappearing for two-thirds of them more than two years after the initial course was given. Researchers published their findings this week in the New England Journal of Medicine.
The treatment consisted of two cycles of immunotherapy before surgery for patients with colon cancer with a specific genetic makeup, known as mismatch-repair deficient or microsatellite instable. The Phase 2 study included 111 patients with non-metastatic, locally advanced and previously untreated dMMR colorectal cancer. They were treated with the monoclonal antibodies Opdivo (nivolumab) and Yervoy (ipilimumab).
At the time of surgery, 95% of patients had 10% or fewer cancer cells remaining. Patients have been monitored in the study by clinicians for well over two years. At this stage in the trial, researchers have detected no live cancer cells in approximately two-thirds of patients. There will be further follow-up, and at three years post treatment patients will be examined to see whether the endpoint of disease-free survival is met at that point in time.
Earlier this year, the manufacturer of Opdivo, Bristol Myers Squibb, announced results evidence indicating successful treatment of patients with metastatic dMMR colon cancer.
In both the non-metastatic and metastatic cancer patients, the cancer cells were cleared by the body’s own immune system. Namely, immunotherapies activate the human body’s immune system to fight cancer. They work by helping to recognize, attack and destroy cancer cells. Besides greater efficacy, experts say a major advantage of such treatments is that patients usually tolerate them better than chemotherapy.
The Dutch news site NOS describes the Phase 2 results for the non-metastatic colorectal cancer patients as groundbreaking. Lead investigator, internist and gastrointestinal oncologist, Myriam Chalabi, suggests “this treatment could be a game-changer.”
Patients with dMMR tumors represent about 10 to 15% of patients with non-metastatic colon cancer. In this subset of patients, the efficacy of chemotherapy is quite limited and is estimated at merely 5%. And so, the effectiveness of dual immunotherapy appears to be much better than chemotherapy prior to surgery.
This specific form of colon cancer contains numerous errors in the DNA, which actually facilitates the immune system’s ability to detect tumor cells. In turn, the immune system goes to work and can successfully eliminate tumor cells.
Colorectal cancer isn’t the only cancer being targeted by the dual immunotherapy, nor the only one featuring the Netherlands Cancer Institute. At the American Society of Clinical Oncology annual meeting this week, researchers from the Institute presented a Phase 3 study which demonstrated that 12-month event-free survival was 83.7% for melanoma patients receiving the Opdivo-Yervoy combination therapy, versus 57.2% for those receiving adjuvant treatment alone.
In addition, investigators presented promising results at ASCO this week from a late stage study evaluating Opdivo plus Yervoy as a first-line treatment for liver cancer.
The dual immunotherapy is showing promise across multiple cancers. And for patients with non-metastatic dMMR colorectal cancer, in particular, the latest findings offer reasons to be optimistic.