Immunotherapy before surgery improves outcomes in colorectal cancer

In 2020, more than 1.9 million people worldwide were diagnosed with colorectal cancer (CR). This figure is projected to increase to 3.2 million cases by 2040.

Some patients with colorectal cancer have tumors that are mismatch repair deficient (dMMR) and microsatellite instability high (MSI-H).

Main aspects and background of the study

Mismatch repair (MMR) is a normal process that occurs in the body’s cells to correct errors during DNA replication. Disruptions in this process can lead to microsatellite instability-high (MSI-H) tumors. Approximately 15% of all colorectal cancer tumors are MSI-H. These tumors can be difficult to treat.

A new clinical trial has found that using the immunotherapy drug pembrolizumab before surgery instead of chemotherapy may improve outcomes for patients with stage 2 or 3 colorectal cancer with MMR deficiency and MSI-H. The study was presented at the 2024 American Society of Clinical Oncology (ASCO) annual meeting.

Focus on Stages 2 and 3 Colorectal Cancer

The study involved 32 patients with stage 2 or 3 colorectal cancer with MMR deficiency and MSI-H. Traditional treatments such as chemotherapy and radiotherapy can prolong life, but do not usually cure the disease, and most patients eventually die from cancer that becomes resistant to these treatments, said Kai-Kin Shiu, FRCP, PhD, consultant oncologist at University College London Hospitals NHS Foundation Trust.

Why pembrolizumab?

The NEOPRISM-CRC phase II clinical trial focused on the immunotherapy drug pembrolizumab, sold under the brand name Keytruda. In June 2020, the US FDA approved the use of pembrolizumab to treat patients with unresectable or metastatic MSI-H or dMMR colorectal cancer.

Main results of the study

Shiu and his team administered three cycles of pembrolizumab, in which a dose of pembrolizumab was given every three weeks, before surgery, instead of the standard treatment of surgery and chemotherapy. The researchers found that more than 50% of participants who received pembrolizumab before surgery were cancer-free after surgery. This is significantly higher than previous studies, where only 4% of participants who received chemotherapy before surgery were cancer-free after surgery.

Conclusion and Next Steps

With these promising results, Shiu said their research now has two main goals:

1. Recruitment of larger numbers of patients to a total of around 70-80 to collect enough data to confirm the three-year relapse-free survival rate.
2. To study the biology of dMMR tumors and the mechanisms of action of immunotherapy to determine in the future which patients will require more or less immunotherapy to achieve long-term remission or cure.

Long-term prospects

Dr. Anton Bilchik, a surgical oncologist and director of the Gastrointestinal and Hepatobiliary Diseases Program at Providence Saint John's Cancer Institute in Santa Monica, California, noted that the study is the first to use immunotherapy at these stages of colorectal cancer before surgery.

Dr. Glenn S. Parker, vice chairman of surgery and chief of colorectal surgery at Hackensack Meridian Jersey Shore University Medical Center, emphasized that long-term follow-up is needed to assess the durability of response to immunotherapy. He also noted that future clinical trials will play an important role in developing molecular genetic profiles for individual patients and their tumors, leading to more precise medicine in the future.

These results highlight the potential for using immunotherapy before surgery to improve outcomes in patients with colorectal cancer.