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5yr

The most commonly mutated oncogene in human cancer is rat sarcoma (RAS), with Kirsten rat sarcoma (KRAS) being the most frequently mutated RAS isoform. In the aggregate, KRAS accounts for 85% of RAS mutations in human cancer, and KRAS exists in 35% of lung adenocarcinomas.



The dysregulation of KRAS results in tumor growth and mediates interactions between cancer cells and the tumor microenvironment, thus impacting therapeutic response. KRAS mutations likely occur early in carcinogenesis and facilitate the survival, invasion, and migration of cancer cells. Smoking has been strongly linked to KRAS mutations in lung cancer.



Previously, KRAS was considered “undruggable” due to difficulty with identifying actionable target-inhibitor binding sites. New developments show that targeting the KRAS 12 glycine to cysteine (G12C) mutation, which depends on covalent modification of the cysteine residue, is effective in the treatment of NSCLC.



What is your experience with KRAS-positive lung cancer? In which patients would you consider KRAS inhibitors?



https://pubmed.ncbi.nlm.nih.gov/34089836/



https://pubmed.ncbi.nlm.nih.gov/34151545/


  • 5yr
    KRAS is a common mutation in NSCLC. Sotorasib is the first drug approved for targeting the KRAS G12C mutation. I had the opportunity to use this only once so far and the experience was positive with a good response and was well tolerated.
  • 5yr
    Only KRAS mutation that is druggable is G12C. Sotorasib recently approved for KRAS G12C patients and has a RR 35% with some CRs.
  • 5yr
    Given the overall frequency of KRAS mutations in NSCLC, particularly G12C, KRAS inhibitors have become new drugs to use in our patients. Sotorasib is a well tolerated agent and allows for an oral TKI option for our patients in second line and beyond. Potential combinations may play a bigger role.
  • 5yr
    Just started first patient on Lumakras. Used in second line as monotherapy. Believe we are just in first inning of kras targeted therapy. Expect additional agents, combination therapy, and first line use in future.
  • 5yr
    I would consider KRAS directed therapy in all mutation positive NSCLC in 2nd line therapy.
  • 5yr
    KRAS often portends poor response to chemo ( chemoresitance) and has been difficult to manage; once KRAS is ositive these patients dont have an other biomarkers positive; it is present more often than otehr biomarkers ad is most common in pancretaic cancer; We have a new drug sotorasib only with G12C; but hope more in near future; I would use a LRAS inhibitor in anyone who cnanot get chemo or progressed or chemo+IO
  • 5yr
    Moving treatment earlier on would be of interest.
  • 5yr
    How would you advise patients on the potential benefits of KRAS inhibitors?
  • 5yr
    Recently we plan to start on one of our patients,I have experience of its use in the trial setting with good tolerance and fair responses. it will be interesting to see combined therapy effects as well.
  • 5yr
    I have not started yet but i expect very positive experience I have about 4 pts with this mutations
  • 5yr
    KRAS is the most common mutation, though not all patients will have G12C, where I will use sotorasib. It will be interesting to see what benefit combination regimens will have with sotorasib.
  • 5yr
    What are your thoughts regarding KRAS G12C monotherapy vs combination therapy? Please see this summarized journal article for more: {{contact.skuid}}
  • 5yr
    For further reading, we provide a summary of a recent review article further examining KRAS G12C monotherapy and potential treatment combinations, as well as resistance and future directions. {{contact.skuid}}
  • 5yr
    I had overall positive experience using KRAS inhibitors for patients with KRAS-positive lung cancer, promising efficacy (survival and response rate data) and favorable safety profile
  • 5yr
    KRAS is the most common targetable alteration in NSCLC. It is also present in COLON ca and RAS targeted therapy would prove useful in other cancers as well. Patients with RAS alteration do as well as other patients. KRAS altered patients with metastatic NSCLC do respond to chemo-immunotherapy. If and when they progress on chemo-immunotherapy, they would be a great candidate for agents such as sotorasib. I have begun to use this agent and seen early responses.

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