Immunotherapy for colorectal cancer
Combination chemotherapy with or without targeted therapy is the key treatment for metastatic colorectal cancer (mCRC). Due to the adverse effects of chemotherapeutic drugs and the biological characteristics of cancer cells, it is difficult to make breakthroughs in traditional strategies. Immune checkpoint blockade (ICB) therapy has made significant progress in the treatment of advanced malignancies, and patients who benefit from this therapy can achieve a durable response.
Unfortunately, immunotherapy is only effective in a limited number of patients with high microsatellite instability (MSI-H), and initial segment responders may later develop acquired resistance. As of September 4, 2014, the first anti-PD-1 / PD-L1 drug Pembrolizumab was approved by the FDA for the second-line treatment of advanced malignant melanoma. Subsequently, it was approved for second-line mCRC treatment in 2017.
Immunotherapy has developed rapidly in the past 7 years. Extensive research of ICB treatment has indicated that the immunoresistance mechanism of colorectal cancer has gradually become clear, and new predictive biomarkers are constantly emerging. Clinical trials examining the effect of immune checkpoints are being actively conducted in order to produce lasting effects for patients with mCRC.
Immune checkpoint inhibitor therapy is relatively less toxic than chemotherapy and targeted therapy. However, some of its unique adverse effects reduce its clinical efficacy, and some rare adverse effects could be life-threatening, resulting in skin, endocrine, liver, gastrointestinal, lung, and skeletal muscle toxicity.
ICBs have been successfully used in the MSI-H CRC population. Pembrolizumab, Nivolumab, and Ipilimumab have been approved for use in refractory MSI-H mCRC, and Pembrolizumab has been recommended as first-line treatment therapy.
More recently, clinical trials have indicated that neoadjuvant immunotherapy may have the potential to become the standard therapy for patients with CRC. In a stepwise exploration, ICBs hold promise as adjuvant therapies for patients with stage III CRC after resection.
In addition, combination with specific drugs is expected to improve efficacy and mitigate associated toxicity. The urgent task is to find more biomarkers and formulate standardized scoring standards in order to select the population and benefit more patients.
In addition to microsatellite status, other potential biomarkers can be developed that can help identify potential populations. More importantly, it is significant to develop measures that can turn "cold tumor" into "hot tumor" so as to expand the scope of immunotherapy. This area of research may provide a milestone in the treatment of CRC.
The purpose of immunotherapy is to stimulate the body's immune system response against cancer cells by targeting specific genetic features.
Patients who have the V600E mutation of the BRAF gene (10-15%) may benefit from the combination of encorafenib (Braftovi®) and cetuximab (Erbitux®) even after a failed attempt with another therapy.
Overexpression of another gene (HER2 neu) is present in 3-5% of colon cancers. Interesting therapeutic results have also been obtained for this alteration with the combination of trastuzumab (Herceptin®) and pertuzumab (Parjeta®) and with trastuzumab deruxetan (Enhertu®). These are treatment options currently available only at highly specialized centers.
