Studying Colon Cancer Treatment
- A new trial is the first study to compare the effectiveness of different targeted drug therapies (panitumumab versus bevacizumab) as part of chemotherapy treatments for a certain kind of colorectal cancer.
- The results of this important trial were presented at the The 2022 American Society of Clinical Oncology (ASCO) annual meeting.
- The study found that the chemo drug folfox plus the drug panitumumab is the preferred choice for patients with a certain kind of metastatic colorectal cancer (left sided).
- The study, known as the PARADIGM trial, is the first phase-III trial to confirm benefits for this specific subset of patients.
Chemotherapy has been very well studied for colorectal cancer and is known to improve survival. The most common therapy is called FOLFOX, and your doctor may add medications like irinotecan (folfiri) depending on how well your tumor shrinks with treatment and other specifics about your particular tumor such as its mutations or sidedness (left versus right). For folfox, the medications are given through the vein and require regular doctor visits. The most common side effects are nausea, diarrhea and numbness in the hands and feet.
Biomarkers Help Determine Colon Cancer Treatment
Read MoreKRAS mutations
Approximately 40-45% of colorectal cancer patients have KRAS mutation in their tumors. This mutation is not hereditary and will not be passed from one generation to another it's completely random. It's important to know if your tumor is KRAS-mutated because positive KRAS-cancers can receive additional treatments such as vascular endothelial growth factor (VEGF) therapy or epidermal growth factor receptor (EGFR) inhibitors.For patients with RAS wild-type disease, the VEGF inhibitor bevacizumab and the EGFR inhibitors panitumumab are all recommended options for use in combination with doublet chemotherapy (FOLFOX) in the first-line setting. However, scant head-to-head data are available to help differentiate between the targeted therapies, especially within the context of tumor sidedness, which can dramatically influence the response to treatment based on various clinicopathologic features.
Despite several retrospective analyses suggesting that anti-EGFR (panitumumab) therapy is superior to VEGF (bevacizumab) therapy in the first-line setting for left-sided metastatic colon cancer with wild-type RAS, bevacizumab continues to be widely used in this population because of the lack of prospective data. The PARADIGM data clearly put this issue to bed says the American Society of Clinical Oncology
Understanding the Paradigm Trial
PARADIGM represents the largest randomized first-line study to prospectively compare the efficacy of different targeted therapies in combination with standard doublet chemotherapy (folfox) based on tumor sidedness.
The study was conducted by Dr. Takayuki Yoshino, MD, PhD, of the National Cancer Center Hospital East, in Japan, and he presented the data for the first time at the Plenary Session of the 2022 ASCO Annual Meeting.
Overall survival (OS) means the time from treatment to death and is the most appropriate measure for clinical trials. OS median was 36.2 months for the patients who received panitumumab with FOLFOX chemotherapy, and 31.3 months for the group who had bevacizumab with FOLFOX chemotherapy.
"This trial demonstrates that, for RAS wild-type and left-sided metastatic colon cancer, the choice of the initial biologic with chemotherapy does matter and that initial treatment with panitumumab with FOLFOX chemotherapy is superior to initial treatment with bevacizumab with FOLFOX chemotherapy," Dr. Yoshino said. "The results from PARADIGM highlight the importance of RAS testing at initial diagnosis of metastatic disease in left-sided CRC and tailoring initial therapy based on the results."
Dr. Chiara Cremolini, MD, PhD, of the University of Pisa, in Italy, reviewed the findings presented at the 2022 ASCO Annual Meeting and notes that PARADIGM represents an important trial for patients with left-sided RAS wild-type metastatic colon cancer.
"From a very practical perspective, I think that a chemotherapy doublet plus an anti-EGFR agent is the preferred choice for patients with left-sided, microsatellite stable, RAS and BRAF wild-type mCRC," Dr. Cremolini explained. "Based on the PARADIGM trial, we are able to share with patients, when they are worried about anti-EGFRrelated adverse events (mainly skin rash), that the choice of a doublet plus bevacizumab would be associated with a 3.6[-month] median loss of OS and a disadvantage in treatment activity."
Given that the PARADIGM trial was conducted in Japan, some might question whether the data can be applied to non-Asian patient populations. Dr. Yoshino refuted this query.
"There is no significant difference between Japanese and non-Japanese patients in terms of efficacy, which has been shown in previous studies," he said. He pointed out that the FIRE-3 trial, which was conducted in Europe to compare cetuximab to bevacizumab in combination with FOLFIRI, showed similar results to PARADIGM, and that pharmacokinetic analyses of panitumumab have identified no significant differences between Japanese and non-Japanese individuals.
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