Preoperative immunotherapy improves outcomes in colorectal cancer

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

Some patients with colorectal cancer have tumors with mating error repair (dMMR) deficiency and microsatellite instability high (MSI-H).

Main aspects and background of the study

Mating error repair (MMR) is a normal process that occurs in the body's cells to correct errors during DNA replication. Disturbances in this process can lead to microsatellite instability-high (MSI-H) tumors. Approximately 15% of all colorectal cancer tumors are MSI-H. Treatment of such tumors can be difficult.

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

Focus on stages 2 and 3 colorectal cancer

The study included 32 patients with stage 2 or 3 colorectal cancer with MMR deficiency and MSI-H. According to Kai-Kin Shiu, FRCP, PhD, consultant oncologist at University College London Hospitals NHS Foundation Trust, 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.

Why pembrolizumab?

The NEOPRISM-CRC Phase II clinical trial focused on the immunotherapy drug pembrolizumab, marketed under the brand name Keytruda. In June 2020, the US FDA approved the use of pembrolizumab for the treatment of 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 until surgery, instead of the standard treatment of surgery and chemotherapy. The researchers found that more than 50% of participants who received pembrolizumab before surgery had no signs of cancer after surgery. This is significantly higher than previous studies, where only 4% of participants who received chemotherapy before surgery were free of cancer after surgery.

Conclusion and next steps

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

1. Recruit more patients to a total of about 70-80 to collect enough data to confirm the three-year recurrence-free survival rate.
2. 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, surgical oncologist and director of the Gastrointestinal and Hepatobiliary Diseases Program at Providence Saint John's Cancer Institute in Santa Monica, California, noted that this study is the first to use immunotherapy at these stages of colorectal cancer before surgery.

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

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