Colon Cancer Immunotherapy Trial Leaves 59% of Patients Cancer-Free After Just Nine Weeks

A clinical trial led by researchers at University College London and University College London Hospitals has found that a short course of the immunotherapy drug pembrolizumab, given before surgery, can leave 59 percent of certain colorectal cancer patients with no detectable disease and has prevented every patient who responded from relapsing for nearly three years. The findings, presented Monday at the American Association for Cancer Research annual meeting in San Diego, are being described by oncologists as one of the most striking results to emerge in a solid-tumor immunotherapy study to date.

The trial enrolled 32 patients with stage two or stage three colorectal cancer whose tumors carried a genetic feature called mismatch repair deficiency, which makes the cancer particularly visible to the immune system. Each patient received pembrolizumab, sold under the brand name Keytruda by Merck, every three weeks for nine weeks before going to the operating room. When surgeons removed the affected portion of the colon, more than half of the resected tissue showed no remaining live cancer cells. After 33 months of follow-up, none of the responders had relapsed.

'These are the kinds of results we dream about and rarely see,' said principal investigator Kai-Keen Shiu of UCL, who led the study. 'For a group of patients who would otherwise face months of intensive chemotherapy and significant surgery, we are seeing the cancer essentially erased before the operating room and staying gone. That is a fundamental change in what early treatment can look like.' The team also developed a personalized blood test, built around each patient's tumor DNA, that successfully detected residual disease before any radiographic signs appeared — raising the prospect that future patients could be monitored noninvasively and avoid the most aggressive surgical interventions when the immunotherapy works.

The approach is limited, for now, to the roughly 15 percent of colorectal cancer patients whose tumors carry the mismatch repair deficiency or its near-equivalent, microsatellite instability. For the remaining majority of colon cancer cases, immunotherapy alone has so far been disappointing, and the standard of care remains surgery followed by chemotherapy regimens such as FOLFOX. Researchers cautioned that the trial was small and that larger phase-three studies will be needed before pembrolizumab can become a recommended pre-surgical regimen. A 250-patient confirmatory trial sponsored by Cancer Research UK is already enrolling at sites across Britain, France and the Netherlands.

The findings add to a growing body of evidence that giving immunotherapy before, rather than after, surgery — an approach known as the neoadjuvant strategy — produces deeper and more durable responses. A separate Memorial Sloan Kettering trial reported in 2022 that all 12 of its rectal cancer patients with the same genetic feature had complete responses to a different immunotherapy. Combined with this week's UCL data, oncologists at the AACR meeting said pre-surgical immunotherapy now appears poised to become the new standard for the subset of colon cancer patients eligible to receive it. 'For these patients, surgery may eventually become optional,' Shiu said. 'That is not a sentence I expected to say in my career.'