Novel immunotherapy combination showed high efficacy among patients with microsatellite stable metastatic colorectal cancer
March 2023 - Results from a phase I study presented at the American So [...]
READ MOREESMO World Congress on Gastrointestinal Cancer 2022
July 2022
The annual ESMO World Congress on Gastrointestinal (GI) Cancer was held this year in Barcelona, Spain, and was dedicated to the presentation and discussion of new findings in GI cancer, providing unique insights into the latest clinical data.
Key highlights from the Congress include:
• The importance of including patient quality of life data in both clinical trials and treatment plans;
• Due to shifting patterns of colorectal cancer in younger adults, there is a growing need to focus attention on prevention and screening of the disease;
• Intensifying cancer treatments does not always result in better outcomes for patients with metastatic CRC – how to balance intensity with sustainability of treatment?
•New practical guidance to promote better outcomes in HER2-positive GI cancers with targeted therapies.
• New recommendations on the use of ctDNA in clinical practice
Colorectal Cancer Study Spotlights:
1. MOUNTAINEER trial: meaningful and durable responses for patients with metastatic HER2-positive colorectal cancer
Findings from the ongoing phase II MOUNTAINEER trial showed that patients with HER2-positive metastatic colorectal cancer (mCRC) who were previously treated with unsuccessful cancer therapies experienced clinically meaningful and long-lasting responses when they were treated with the combination of targeted therapies: tucatinib plus trastuzumab.
The lead investigator Dr. John Strickler noted that patients with HER2-positive mCRC receive limited clinical benefits with currently available therapies including chemotherapy. The novel combination of targeted therapies, tucatinib and trastuzumab, resulted in sustained responses and was well-tolerated in heavily pretreated patients (i.e. those that progressed on first- and second-line chemotherapy). These findings highlight the combination as a potential new treatment option for patients with HER2-positive mCRC in this setting.
Tucatinib and trastuzumab
In patients with HER2-positive CRC, the HER2 gene is mutated or changed, resulting in overexpression of the HER2 receptor on the cell surface. This results in over proliferation of cells, eventually resulting in cancer.
Tucatinib and trastuzumab are both drugs that specifically target the mutated HER2 protein receptor, interfering with the cell proliferation process.
Patients with HER2+, RAS wild type mCRC who had progressed on previous treatment including chemotherapy, anti-VEGF targeted therapy, and anti-PD1 immunotherapy were included in the study. Patients who had received previous HER2-directed therapies were not included in the trial.
Patients received either a combination of tucatinib and trastuzumab, or tucatinib alone with the option of crossing over to the combination therapy if the disease worsens at any time.
At median follow-up (20.7 months), the study findings demonstrated that the combination of targeted therapies resulted in a promising overall response rate (38.1%) with a median duration of response of 12.4 months. Median progression-free survival was 8.2 months, and median overall survival was 24.1 months.
Data from the MOUNTAINEER trial will be used to support a new drug application in the US for patients with mCRC.
2. Results from the CheckMate 142 study: long-term benefit of combination immunotherapy in previously treated MSI-H/dMMR mCRC
About 5% of patients MSI-H/dMMR mCRC and suffer poor outcomes when treated with chemotherapy in the second-line setting (i.e. after initial treatment has failed), experiencing a median overall survival of less than 16 months. This underlines the need for better treatment options for this subgroup of patients in later lines of treatment.
The immunotherapy drug nivolumab given in combination with another immunotherapy agent, ipilimumab, resulted in long-lasting clinical benefit over 4 years of follow-up in the CheckMate 142 study in which patients experienced high response rates, low rates of disease progression, and a long-term survival benefit.
The CheckMate 142 study involves the longest duration of follow-up reported for the combination of two immune checkpoint inhibitors in patients who have been previously treated for microsatellite instability high (MSI-H)/mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC). The findings confirm that this combination does provide long-term clinical benefit and will support the use of this combination as standard of care for this subgroup of patients.
