Researchers examined whether the PD-1 inhibitor pembrolizumab given neoadjuvantly may improve outcomes in certain patients with stage II or III mismatch repair–deficient/microsatellite instability–high colorectal cancer. Interim findings from the phase II NEOPRISM-CRC clinical trial were presented by Shiu et al at the 2024 ASCO Annual Meeting (Abstract LBA3504).
Background
Although colorectal cancer still predominantly affects older patients, cases have been rising among patients younger than 50 years in recent decades.
When colorectal cancer is detected in its earliest stages, there is about a 90% rate of 5-year survival following treatment. However, certain subtypes of colorectal cancer don’t respond to therapy and are more likely to recur. In patients with stage III or IV colorectal cancer, the rate of 5-year survival falls to 65% and 10%, respectively.
About 10% to 15% of patients with stage II or III colorectal cancer have mismatch repair–deficient/microsatellite instability–high disease.
Study Methods and Results
In the new trial (ClinicalTrials.gov identifier NCT05197322), the researchers assigned 32 patients with stage II or III mismatch repair–deficient/microsatellite instability–high colorectal cancer to receive 9 weeks of pembrolizumab prior to surgery instead of the standard chemotherapy and surgery. They were monitored over time. The researchers also evaluated whether tumor mutation burden could be a useful biomarker to predict individual patients’ risk.
The researchers found that 59% of the patients who received pembrolizumab prior to surgery presented with no signs of cancer following treatment with pembrolizumab. The remaining 41% of patients had their tumors removed during surgery.
Additionally, 100% of the patients involved in the trial were cancer-free following treatment and have not experienced disease recurrence months later. The median cancer-free period was 9.7 months and ranged from 5.3 to 19.0 months among individual patients. When standard of care conventional chemotherapy is administered in patients with this genetic profile, less than 5% of them are cancer-free following surgery.
The researchers noted that with the new approach, patients didn’t require postoperative chemotherapy, which often comes with side effects.
Conclusions
“Our results indicate that pembrolizumab is a safe and highly effective treatment to improve outcomes in patients with high-risk [colorectal] cancer, increasing the chances of curing the disease at an early stage,” highlighted lead study author Kai-Keen Shiu, FRCP, PhD, of the University College London Cancer Institute and a consultant medical oncologist at the University College London Hospitals National Health Service (NHS) Foundation Trust. “We need to wait to see whether the patients in our trial remain cancer-free over a longer period of time, but initial indications are extremely positive,” he added.
“This is a … very exciting new treatment for the … patients who have the right genetic make-up. Immunotherapy prior to surgery could well become a gamechanger for these patients with this type of cancer. Not only is the outcome better, but it saves patients from having more conventional chemotherapy, which often has more side effects,” emphasized Mark Saunders, MBBS, MRCP, FRCR, PhD, a consultant clinical oncologist at The Christie NHS Foundation Trust. “In the future, immunotherapy may even replace the need for surgery. However, more trials are needed to confirm these exciting early results … so that we can offer this new [type] of therapy to our patients as part of the NEOPRISM-CRC trial,” he suggested.
Over a follow-up period of 5 years, the researchers plan to assess overall survival and relapse rates.
“More work needs to be done to assess pembrolizumab before it could be considered standard treatment, but given the quality of the outcomes in this trial, [we] think it’s possible that we could see it in the clinic within a couple of years if subsequent trials are similarly successful,” concluded senior study author Marnix Jansen, MD, PhD, a clinician scientist and consultant histopathologist at the University College London Cancer Institute and University College London Hospitals NHS Foundation Trust.
Disclosure: The research in this trial was funded by Merck Sharp and Dohme and sponsored by the University College London. For full disclosures of the study authors, visit meetings.asco.org.
