Patients with metastatic colorectal cancer may continue to benefit from immunotherapy even after treatment is discontinued

The majority of patients with metastatic colorectal cancer whose cancer did not progress during initial treatment with immune checkpoint inhibitors (ICIs) had no disease progression for two years after stopping treatment, a new study reports. There is.

Research is published in a diary cancer research communication.

ICIs have proven effective against certain solid tumors, including those with microsatellite instability (MSI-H) and DNA mismatch repair (dMMR)-deficient states. To date, four ICIs have been approved by the US Food and Drug Administration (FDA) for the treatment of advanced MSI-H/dMMR colorectal cancer.

If a patient’s colorectal tumor shrinks or remains stable during ICI treatment, the doctor may stop immunotherapy after 2 years. Some patients may also discontinue ICI treatment prematurely due to unmanageable side effects. Dr. Morris explained that if patients stop a treatment plan that has been working, they may worry that it will no longer be effective.

“Patients are understandably worried about discontinuing a treatment that appears to be effective and does not cause many side effects. They have been diagnosed with stage 4 colorectal cancer and “I have questions about the possibility that my cancer will come back if I stop treatment,” Morris said. “When we started this study, we didn’t know the odds.”

Morris et al. studied 64 patients with MSI-H/dMMR metastatic colorectal cancer treated with ICIs targeting PD-1 or PD-L1 alone (n = 48) or in combination with ICIs targeting CTLA-4. A retrospective analysis was conducted (16 patients). All patients were experiencing sustained effects at the time of treatment discontinuation. Forty-eight patients discontinued treatment due to long-lasting effects, and 16 discontinued treatment due to side effects. Patients had been on ICI therapy for a median of 17.6 months.

At a median of 22.6 months after stopping immunotherapy, 88% of patients had not experienced recurrence. Progression-free survival after stopping immunotherapy was 98% at 1 year, 91% at 2 years, and 84% at 3 years after treatment. There were no significant differences in rates whether patients discontinued treatment due to side effects or prolonged response.

Researchers investigated other factors that may influence the likelihood of relapse after treatment is discontinued. No significant differences in progression rates were observed whether patients received her ICI monotherapy or combination therapy. Presence of metastasis to the liver, peritoneum, or lymph nodes. and whether the tumor has mutations in KRAS, NRAS, or BRAF. Patients with lung metastases were more likely to have a recurrence than those without lung metastases, a finding that warrants further investigation, Morris said.

Seven of the eight patients whose tumors progressed after discontinuing treatment were returned to ICI therapy. Of note, all seven patients experienced response or stable disease after rechallenge with ICI.

Professor Morris suggested that these data could ease the fears of doctors who do not want to stop treating patients because of the high-risk characteristics of their tumors. “We often hear from oncologists that they are reluctant to stop treatment in patients with, for example, a BRAF mutation.However, we do not see a link between mutational status and the likelihood of cancer recurrence. Professor Morris said:

“These data provide important information for oncologists to guide discussions with patients with MSI-H/dMMR colorectal cancer and assess the likelihood of progression if the patient decides to discontinue immunotherapy treatment. “This provides clearer numbers on the current situation,” he continued. “Based on these data, if we tell patients that there is an 88% chance that their cancer will not come back if they stop treatment, they may be more accepting of the decision to stop treatment.”

Limitations of this study include its retrospective nature as well as the relatively small sample size, which limits the statistical power of subgroup analyses. Furthermore, this cohort included patients from a single cancer center, which may limit the applicability of the data to patients at other locations.