Study Shows Continuing Benefit After Stopping Immunotherapy

Progression-free survival among certain patients with metastatic colorectal cancer continued at a high level after immune checkpoint inhibitor therapy was stopped.

Some patients with metastatic colorectal cancer who benefit from immunotherapy are reluctant to discontinue the treatment when recommended by their doctors. New findings published in the AACR journal Cancer Research Communications suggest that stopping the treatment doesn’t mean patients lose its benefits. 

The study was conducted to see if the benefits experienced by the patients during their treatment continued after the therapy was stopped due to side effects or after the recommended duration of treatment. The study included 64 patients with tumors characterized by high microsatellite instability (MSI-H) or deficient DNA mismatch repair (dMMR). To date, four immune checkpoint inhibitors—common forms of immunotherapy—have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced MSI-H/dMMR colorectal cancer.

Results of the study showed that the progression-free survival rate after cessation of immunotherapy was 98% at one year, 91% at two years, and 84% at three years post-treatment, indicating that the benefit of the immunotherapy continued after it was stopped. 

“Patients very understandably get afraid at the prospect of stopping a therapy which appears to be working and often does not cause many side effects,” said Van Morris, MD, senior author of the study and an associate professor in the Department of Gastrointestinal Medical Oncology at the University of Texas MD Anderson Cancer Center.

“They’ve had a diagnosis of stage 4 colorectal cancer, and they wonder about the chance of their cancer coming back if they stop treatment,” Dr. Morris said. “When we set out to do this study, we didn’t know the odds.”

All 64 patients in the study had experienced a durable benefit by the time the immunotherapy treatment was stopped. Among 48 patients, the treatment was discontinued because of prolonged benefit, and 16 discontinued treatment due to side effects. Patients received immunotherapy for a median of 17.6 months.

“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,” Dr. Morris said. “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 of therapy, I think they may be more accepting of that decision to stop treatment.”

The findings may also provide guidance to physicians who are concerned that their patients’ tumors have high-risk characteristics that may need continued immunotherapy.

In fact, no significant differences in progression rates were observed whether patients received single-agent or combination ICI therapy; whether or not they had metastases to the liver, peritoneum, or lymph nodes; and whether or not their tumors had mutations in KRAS, NRAS, or BRAF. Patients with lung metastases had a higher chance of recurrence than patients without lung metastases, a finding Dr. Morris said requires further investigation.

“We often hear from oncologists that they don’t feel comfortable stopping treatment on a patient with a BRAF mutation, for instance. But we did not see any association between mutation status and the likelihood for the cancer to recur,” Dr. Morris said.

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