scispace - formally typeset
Search or ask a question

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

Best insight from top research papers

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 .

Answers from top 5 papers

More filters
Papers (5)Insight
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.

See what other people are reading

What is Mendelian genetics?
4 answers
Mendelian genetics, established by Gregor Mendel in the 19th century, is the study of genetic inheritance patterns in organisms based on the principles of heredity he proposed. Mendel's meticulous experimental design and observations led to the formulation of the fundamental laws of inheritance, known as Mendelian rules. These rules serve as the cornerstone of genetics, guiding our understanding of how traits are passed down from parents to offspring. Furthermore, the concept of Mendelian randomization, a modern epidemiological method, utilizes genetic variants as instrumental variables to investigate causal relationships between modifiable exposures and outcomes, building upon Mendel's laws of inheritance. Mendelian genetics continues to play a crucial role in unraveling the complexities of genetic inheritance and its implications for various fields of study.
How effective is intravitreal injection of anti-VEGF drugs in delaying visual deterioration in patients with diabetic macular edema?
5 answers
Intravitreal injection of anti-VEGF drugs, such as ranibizumab, aflibercept, and brolucizumab, has shown effectiveness in delaying visual deterioration in patients with diabetic macular edema (DME). Studies have demonstrated that anti-VEGF therapy leads to significant improvements in best-corrected visual acuity (BCVA) and reduction in central macular thickness (CMT) in DME patients, thereby delaying visual impairment. Additionally, the use of sustained-release devices like the Port Delivery System and biodegradable drugs aims to reduce the frequency of injections and prolong the drug's effect, further enhancing the treatment outcomes for DME. Overall, intravitreal anti-VEGF therapy has proven to be safe and effective in managing DME, highlighting its role in preserving vision and preventing visual deterioration in affected individuals.
What are the weaknesses of establishing Filipino food cuisines in California?
5 answers
Establishing Filipino food cuisines in California faces challenges due to historical and social contexts. The economic struggles and racial politics faced by Filipino immigrants in the U.S. hindered their integration and acceptance. Additionally, the complexities of Filipino-American legal status and the conflicts with local nativists and agribusiness interests created barriers to full assimilation and acceptance. Moreover, the lack of consideration for Filipinos in existing racial categories and the conflicting interests of different societal groups further complicate the establishment of Filipino food cuisines in California. These historical and social challenges highlight the difficulties in promoting and popularizing Filipino cuisine in California, reflecting broader issues of acceptance and integration faced by Filipino immigrants in the U.S.
Is competition or collaboration a better strategic choice for businesses operating in a permacrisis world?
5 answers
In a permacrisis world, businesses face the dilemma of choosing between competition and collaboration. Research suggests that a balance between competition and collaboration is crucial. While competition can drive innovation and efficiency, collaboration is essential for resilience and resource optimization. The interconnected nature of global challenges, such as the COVID-19 pandemic, highlights the importance of collaborative approaches in managing crises effectively. Coopetition, a concept involving simultaneous cooperation and competition with competitors, has emerged as a strategic choice for businesses to navigate complex and uncertain environments. By engaging in both internally and externally focused coopetition, firms can develop new knowledge-based resources and capabilities, enhancing their competitiveness while mitigating risks associated with opportunistic behaviors. Ultimately, a strategic blend of competition and collaboration, exemplified by coopetition, seems to offer a promising approach for businesses in a permacrisis world.
What is selective breeding?
5 answers
Selective breeding is a method that involves intentionally choosing individuals with desired traits to be parents of the next generation, aiming to enhance specific characteristics in subsequent offspring. This technique has been successfully applied across various species, including flies, corals, rabbits, zebrafish, and tea plants. By selectively breeding for extreme phenotypes, researchers can explore the genetic networks influencing targeted traits, discover correlated responses of traits with shared genetic architecture, and identify naturally occurring genomic variants and gene expression changes. Selective breeding has been shown to increase stress tolerance, growth speed, meat output, disease resistance, and bioactive ingredient contents in different organisms. It is a valuable tool for studying genetic and developmental resilience, as well as for conservation efforts in the face of challenges like climate change.
Consumer preferences affecting checkout abandonment?
4 answers
Consumer preferences play a crucial role in checkout abandonment in online shopping. Various factors influence this behavior, such as consumers using shopping carts for research and entertainment purposes, having abstract mindsets leading to higher purchase intentions, waiting for lower prices impacting hesitation at checkout and subsequent abandonment, and the relationship between research purpose, entertainment purpose, perceived cost, perceived risk, transaction inconvenience, and abandonment being partially mediated by pre-decisional conflict. Additionally, the development of machine learning systems can predict checkout outcomes based on customer activity, aiding merchants in reducing abandonment rates and making informed decisions. Understanding these consumer preferences is essential for online retailers to implement strategies that reduce checkout abandonment and enhance the overall shopping experience.
What are new trends or future of object detection?
5 answers
The future of object detection lies in advancements such as Future Object Detection, which focuses on predicting bounding boxes for objects in future video frames. This involves capturing temporal, kinematic, semantic, and geometric patterns using end-to-end methods like detection transformers. Additionally, the integration of deep learning methods, particularly convolutional neural networks (CNNs) and transformer-based detectors, has revolutionized object detection by eliminating the need for hand-crafted feature extraction processes. These models show superior real-time performance and accuracy, paving the way for set prediction techniques and enhanced detection modes. The continuous evolution of algorithms like R-CNN, fast R-CNN, faster R-CNN, YOLO, corner net, and NAS further propels object detection towards higher precision, reduced computational complexity, and faster detection speeds.
What is the difference between free electronics activities and wave electronics activities?
4 answers
Free electronics activities involve accelerating charged particles using methods like plasma wave accelerators and inverse free electron lasers, where electrons are accelerated by an intense laser field and a static magnetic field, leading to strong acceleration and ejection tendencies when using a focused laser beam. On the other hand, wave electronics activities focus on decentralized trust in authorization systems, like the WAVE framework, which ensures that permissions cannot be modified or seen by central services, allowing participants to autonomously delegate permissions securely. WAVE employs cryptographic enforcement, novel encryption protocols, and untrusted scalable storage solutions to protect permissions while offering competitive performance to traditional centralized systems. Both types of activities showcase innovative approaches in their respective fields, with free electronics emphasizing particle acceleration and wave electronics emphasizing secure decentralized authorization.
How do spectrometric techniques contribute to the detection and prevention of food fraud?
4 answers
Spectrometric techniques play a crucial role in detecting and preventing food fraud by providing rapid, non-destructive, and cost-effective means of analyzing food authenticity. These techniques, such as hyperspectral imaging, NMR, Raman, IR, UV, visible, fluorescence, and X-ray-based methods, offer efficient ways to verify the quality and origin of food products. By utilizing advanced spectroscopic methods in combination with chemometric tools, it becomes possible to extract relevant information, handle complex data, and ensure the accuracy of food analysis. The integration of spectrometric techniques with specialized algorithms and machine learning models further enhances the ability to differentiate between pure and adulterated food products, such as olive oil, even in challenging environments. Overall, the application of spectrometric techniques in food analysis contributes significantly to safeguarding consumer health, ensuring product quality, and combating fraudulent practices in the food industry.
How does the choice of coding method affect the accuracy and reliability of qualitative analysis?
5 answers
The choice of coding method significantly impacts the accuracy and reliability of qualitative analysis. Coding is a fundamental step in qualitative research, involving the systematic organization and interpretation of data. Different coding techniques, such as open coding or using software tools like QualCoder, influence the depth and rigor of the analysis process. Intercoder reliability, as demonstrated through techniques like the Many Facet Rasch Model (MFRM), plays a crucial role in ensuring consistency and trustworthiness in qualitative data analysis. The method chosen for coding can affect the transparency, efficiency, and overall quality of the analysis, ultimately impacting the validity of the findings and the development of theory in qualitative research.
What is the criteria for diagnosis of DKA?
4 answers
The diagnostic criteria for Diabetic Ketoacidosis (DKA) include elevated blood glucose levels, metabolic acidosis with a pH <7.3, serum bicarbonate <18 mEq/L, and the presence of ketones in the blood or urine. Additionally, anion gap metabolic acidosis is a key indicator for diagnosing DKA. Other factors such as elevated beta-hydroxybutyrate levels, decreased serum bicarbonate, and glucose levels >200 mg/dL are also considered in the diagnosis of DKA. It is crucial to differentiate DKA from other conditions like hyperosmolar hyperglycemic syndrome (HHS) and euglycemic DKA to ensure accurate diagnosis and appropriate management.