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What are the treatment patterns for third line therapy in KRAS G12C-mutated CRC colorectal cancer? 


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In KRAS G12C-mutated colorectal cancer (CRC), third-line therapy typically involves various treatment patterns. Patients with this mutation often receive systemic therapy, with a significant proportion undergoing surgical resection in the metastatic setting. In later lines of therapy, outcomes, particularly real-world progression-free survival (rwPFS), tend to be poorer. Notably, patients with co-mutations like FBXW7 may experience shorter overall survival (OS), while those with PIK3CA co-mutations might have longer rwPFS compared to those with KRAS G12C alone . Combination therapies have shown promise in suppressing CRC cell growth, with inhibitors targeting KRAS G12C, EGFR, and FGFR, or KRAS G12C and SHP2, demonstrating effectiveness . Additionally, the combination of a KRAS G12C inhibitor with an anti-EGFR antibody like cetuximab has shown greater anti-tumor activity than monotherapy in preclinical models, highlighting the potential for robust clinical benefit in patients with KRAS G12C-positive CRC .

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Combination therapy of KRAS G12C and EGFR inhibitors shows promise in third-line treatment for KRAS G12C-mutated CRC, with potential resistance mechanisms like KRAS G12C amplification identified.
KRAS G12C-mutated CRC may benefit from emerging targeted therapies. The paper discusses advancements in targeted therapies for metastatic CRC, emphasizing the potential of KRAS p.G12C as a therapeutic target.
In KRAS G12C-mutated CRC, third-line therapy includes GDC-6036 and cetuximab combination, showing a manageable safety profile and promising clinical activity with a 62% confirmed overall response rate.
In KRAS G12C-mutated CRC, third-line therapy commonly involved oxaliplatin- or irinotecan-based regimens. Median rwPFS from the start of third-line therapy was 3.1 months.
Combination therapy with KRAS G12C, EGFR, and FGFR inhibitors or KRAS G12C and SHP2 inhibitors shows efficacy in overcoming resistance in KRAS G12C-mutated CRC third-line therapy.

Related Questions

What is the incidence and prevalence for second line and third line KRAS G12C-mutated colorectal cancer?5 answersThe prevalence of KRAS G12C mutation in colorectal cancer (CRC) is estimated to be around 3.1% globally, with a range of 0.7%-14%. In the context of second and third-line treatments, the prevalence of KRAS G12C mutation in CRC patients undergoing targeted sequencing was found to be 3.11%. Additionally, the KRAS G12C mutation is associated with a worse prognosis in metastatic CRC, indicating the need for targeted therapies. The data suggests that KRAS G12C mutations are more common in certain subsets of CRC patients, highlighting the importance of personalized treatment strategies for this specific mutation in advanced stages of the disease.
What is the current understanding of the epidemiology of second line and third line KRAS G12C-mutated colorectal cancer (CRC)??5 answersThe epidemiology of second and third-line KRAS G12C-mutated colorectal cancer (CRC) reveals crucial insights. KRAS mutations are prevalent in CRC, with the G12C mutation occurring in approximately 3% of patients. In advanced PDAC patients with KRAS G12C mutations, those treated with gemcitabine and nab-paclitaxel (GP) had significantly longer median overall survival compared to those receiving FOLFIRINOX. Additionally, a study in the Argentine population found a prevalence of 14.48% for KRAS G12C mutations, with associations noted between clinical variables like disease stage and smoking status. Understanding the distinct prognostic implications of KRAS mutations, particularly the G12C mutation, is crucial for tailoring treatment strategies in advanced CRC patients.
What is the current understanding of the unmet needs of 3L treatment in KRAS G12C-mutated colorectal cancer (CRC)??5 answersThe current understanding of the unmet needs in the 3L treatment of KRAS G12C-mutated colorectal cancer (CRC) revolves around the limited treatment options for advanced disease. While KRAS mutations, particularly G12C, are prevalent in CRC and historically considered "undruggable," recent breakthroughs with specific inhibitors like Sotorasib and Adagrasib have shown promising efficacy in metastatic CRC. However, challenges such as drug resistance have been observed, leading to the exploration of combination strategies to enhance treatment effectiveness. The emergence of novel KRAS-targeted therapies, including those targeting KRAS G12C, signifies a paradigm shift in CRC management, offering hope for improved outcomes in patients with this mutation. Further research and clinical trials are underway to address these unmet needs and optimize treatment strategies for KRAS G12C-mutated CRC patients.
What are the total costs associated with KRAS G12C-mutated col?5 answersThe total costs associated with KRAS G12C-mutated colorectal cancer (CRC) can vary based on different factors such as testing strategies and treatment regimens. Studies have shown that predictive testing for KRAS mutations, like KRAS G12C, before administering EGFR inhibitors can lead to cost savings in the treatment of metastatic CRC. Additionally, nationwide studies have highlighted the costs of molecular testing for KRAS status, showing that reagent costs per patient ranged from €5.5 to €19.0. In the context of non-small cell lung cancer (NSCLC), where KRAS G12C is common, real-world analyses have indicated that patients with this mutation may have worse outcomes with certain treatment combinations, potentially impacting overall costs. Therefore, the total costs associated with KRAS G12C-mutated CRC can be influenced by testing strategies, treatment choices, and patient outcomes.
What are the most effective treatments for colorectal cancer?4 answersThe most effective treatments for colorectal cancer include surgery, chemotherapy, immunotherapy, and targeted therapy. Surgery is a common treatment method for both primary and advanced colorectal cancer. Chemotherapy and radiotherapy are also widely used, but their effectiveness is limited, leading to a high mortality rate and low survival rate. Immunotherapy, such as immune checkpoint blockade and adoptive cell therapy, has shown promising results in preclinical and clinical studies. Targeted therapy, specifically immune checkpoint inhibitors and neoantigens-based therapies, have shown significant improvements in the treatment of advanced colorectal cancer. Additionally, combination treatments using immune checkpoint inhibitors before surgery have shown positive outcomes. These innovative treatment methods aim to improve patient outcomes, minimize toxicity, and prevent acquired resistance in colorectal cancer treatment.
What are the implications of a KRAS mutation for the treatment of colorectal cancer?3 answersKRAS mutations have significant implications for the treatment of colorectal cancer (CRC). These mutations are frequently observed in CRC, particularly in codons 12 and 13, and are associated with oncogenic properties. Mutations in KRAS lead to abnormal activation of KRAS proteins, which stimulate signals involved in cancer-related processes such as cell proliferation, migration, and neoangiogenesis. Historically, KRAS mutations were considered "undruggable" and associated with resistance to EGFR targeted therapy. However, the development of allele-specific covalent KRAS G12C inhibitors has made a breakthrough in KRAS targeted therapy, particularly in CRC. Additionally, the presence of the KRAS G13D mutation has been found to negatively impact the prognosis and survival outcome of CRC patients, suggesting the need for tailored surveillance and treatment strategies for these patients. Overall, understanding the implications of KRAS mutations in CRC is crucial for developing effective targeted therapies and improving patient outcomes.

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