Excluding skin cancers, colorectal cancer is the third most common cancer diagnosed in both men and women in the United States, and the third-leading cause of cancer-related deaths. According to the American Cancer Society, in 2023, it is estimated that about 52,550 individuals died from the disease.
Although immune checkpoint inhibitors improve survival in patients with mismatch repair–deficient/microsatellite instability–high (dMMR/MSI-H) colorectal cancer, outcomes once immunotherapy treatment is stopped after disease control is achieved remain unknown. In a retrospective study by Simmons et al published in Cancer Research Communications, the majority of patients with metastatic colorectal cancer whose disease did not progress during initial treatment with immune checkpoint inhibitors had no disease progression 2 years after treatment ended. Favorable outcomes for these patients were observed regardless of the reason for stopping treatment or a variety of patient and disease features.
Study Methodology
Researchers performed a retrospective analysis of 64 patients with dMMR/MSI-H metastatic colorectal cancer who were treated at The University of Texas MD Anderson Cancer Center between 2014 and 2022 with an immune checkpoint inhibitor targeting PD-1 or PD-L1, either as a monotherapy (n = 48) or in combination with an immune checkpoint inhibitor targeting CTLA-4 (n = 16). The median patient age was 64 years.
KEY POINTS
- The majority of patients with metastatic colorectal cancer whose cancer did not progress during initial treatment with immune checkpoint inhibitors had no disease progression 2 years after treatment ended.
- Favorable outcomes were observed regardless of the reason for stopping treatment or a variety of patient and disease features.
All of the patients had experienced a durable benefit at the time of treatment cessation. Forty-eight patients discontinued treatment due to a prolonged benefit, and 16 discontinued treatment due to side effects. The patients received immunotherapy for a median of 17.6 months.
Results
The researchers found that at a median follow-up of 22.6 months (range = 0.3–71.7 months) after stopping immunotherapy, 56 of 64 patients (88%) remained without disease progression. Lung metastases were associated with recurrence/progression (odds ratio = 6.1, P = .04), but coexisting mutations, primary tumor sidedness, and immunotherapy were not.
“These data provide a retrospective, single-institution analysis that showed that most patients with advanced MSI-H colorectal cancer do not recur after treatment cessation, regardless of the reason for stopping treatment or a variety of patient and disease features, supporting an optimistic prognosis of sustained disease control,” concluded the study authors.
Clinical Significance
“These data provide important information that oncologists can use for guiding discussions with patients with MSI-H/dMMR colorectal cancer by providing clearer numbers for the likelihood of progression should they decide to stop their immunotherapy treatment,” said senior study author Van Karlyle Morris, MD, Associate Professor in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center. “If you tell patients that, based on these data, there’s an 88% chance that their cancer won’t come back if they come off therapy, I think they may be more accepting of that decision to stop treatment.”
Dr. Morris, of The University of Texas MD Anderson Cancer Center, is the corresponding author of this study.
Disclosure: Funding for this study was provided by the National Cancer Institute, Cancer Prevention and Research Institute of Texas, Andrew Sabin Fellow Family Foundation, and the Col. Daniel Connelly Memorial Fund. For full disclosures of the study authors, visit aacrjournals.org/cancerrescommun.
